Skip to main content

Advertisement

SpringerLink
Log in

Role of purines in regulation of metabolic reprogramming

  • Review Article
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

Purines, among most influential molecules, are reported to have essential biological function by regulating various cell types. A large number of studies have led to the discovery of many biological functions of the purine nucleotides such as ATP, ADP, and adenosine, as signaling molecules that engage G protein-coupled or ligand-gated ion channel receptors. The role of purines in the regulation of cellular functions at the gene or protein level has been well documented. With the advances in multiomics, including those from metabolomic and bioinformatic analyses, metabolic reprogramming was identified as a key mechanism involved in the regulation of cellular function under physiological or pathological conditions. Recent studies suggest that purines or purine-derived products contribute to important regulatory functions in many fundamental biological and pathological processes related to metabolic reprogramming. Therefore, this review summarizes the role and potential mechanism of purines in the regulation of metabolic reprogramming. In particular, the molecular mechanisms of extracellular purine- and intracellular purine-mediated metabolic regulation in various cells during disease development are discussed. In summary, our review provides an extensive resource for studying the regulatory role of purines in metabolic reprogramming and sheds light on the utilization of the corresponding peptides or proteins for disease diagnosis and therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314

    CAS  PubMed  Google Scholar 

  2. Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8(6):519–530

    PubMed  PubMed Central  Google Scholar 

  3. Ramaiah A (1974) Pasteur effect and phosphofructokinase. Curr Top Cell Regul 8:297–345

    CAS  PubMed  Google Scholar 

  4. Yoshida GJ (2015) Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res 34(1):1–10

    Google Scholar 

  5. Krebs HA (1972) The Pasteur effect and the relations between respiration and fermentation. Essays Biochem 8(1):1

    CAS  PubMed  Google Scholar 

  6. Ward PS, Thompson CB (2012) Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 21(3):297–308

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Libby CJ (2018) The Pro-tumorigenic Effects of Metabolic Alterations in Glioblastoma Including Brain Tumor Initiating Cells. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1869(2):175–188

    CAS  Google Scholar 

  8. Herranz D et al (2015) Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in acute lymphoblastic leukemia. Nat Med 21(10):1182

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Rozovski U et al (2016) Metabolism pathways in chronic lymphocytic leukemia. Leuk Lymphoma 57(4):758–765

    CAS  PubMed  Google Scholar 

  10. Boroughs LK, Deberardinis RJ (2015) Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol 17(4):351–359

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Aguilar E et al (2016) Metabolic reprogramming and dependencies associated with epithelial cancer stem cells independent of the epithelial-mesenchymal transition program. Stem Cells 34(5):1163

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wettersten HI, Hakimi AA, Morin D, Bianchi C, Johnstone ME, Donohoe DR, Trott JF, Aboud OA, Stirdivant S, Neri B, Wolfert R, Stewart B, Perego R, Hsieh JJ, Weiss RH (2015) Grade-dependent metabolic reprogramming in kidney cancer revealed by combined proteomics and metabolomics analysis. Cancer Res 75(12):2541–2552

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Chang HJ et al (2009) GLUT1 gene is a potential hypoxic marker in colorectal cancer patients. BMC Cancer 9(1):241

    PubMed  PubMed Central  Google Scholar 

  14. Dong J, Xiao D, Zhao Z, Ren P, Li C, Hu Y, Shi J, Su H, Wang L, Liu H, Li B, Gao P, Qing G (2017) Epigenetic silencing of microRNA-137 enhances ASCT2 expression and tumor glutamine metabolism. Oncogenesis 6(7):e356

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Deberardinis RJ et al (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7(1):11–20

    CAS  PubMed  Google Scholar 

  16. Søreide K, Sund M (2015) Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer. Cancer Lett 356(2):281–288

    PubMed  Google Scholar 

  17. Sinclair LV et al (2013) Corrigendum: control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat Immunol 14(5):500–508

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Zeng H (2013) T cell exit from quiescence and differentiation into Th2 cells depend on raptor-mTORC1-mediated metabolic reprogramming. Immunity 39(6):1043–1056

    PubMed  PubMed Central  Google Scholar 

  19. Ryall JG, Cliff T, Dalton S, Sartorelli V (2015) Metabolic reprogramming of stem cell epigenetics. Cell Stem Cell 17(6):651–662

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Eng CH, Abraham RT (2011) The autophagy conundrum in cancer: influence of tumorigenic metabolic reprogramming. Oncogene 30(47):4687–4696

    CAS  PubMed  Google Scholar 

  21. Subhra NBSP, Biswas K (2015) Metabolic reprogramming of immune cells in cancer progression. Immunity 43(3):435

    Google Scholar 

  22. Kelly B, O'Neill LA (2015) Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res 25(7):771–784

    PubMed  PubMed Central  Google Scholar 

  23. Torigoe M, Iwata S (2017) Metabolic Reprogramming Commits Differentiation of Human CD27(+)IgD(+) B Cells to Plasmablasts or CD27(-)IgD(-) Cells. J Immunol 199(2):425–434

  24. Deng J et al (2016) Homocysteine activates B cells via regulating PKM2-dependent metabolic reprogramming. J Immunol 198(1):170

    PubMed  PubMed Central  Google Scholar 

  25. Al-Khami AA, Rodriguez PC (2016) Metabolic Reprogramming of Myeloid-derived Suppressor Cells (MDSC) in Cancer. OncoImmunology 5(8):e1200771

    PubMed  PubMed Central  Google Scholar 

  26. Keating SE, Zaiatz-Bittencourt V, Loftus RM, Keane C, Brennan K, Finlay DK, Gardiner CM (2016) Metabolic reprogramming supports IFN-γ production by CD56bright NK cells. J Immunol 196(6):2552–2560

    CAS  PubMed  Google Scholar 

  27. Hsu YC, Chen CT, Wei YH (2016) Mitochondrial resetting and metabolic reprogramming in induced pluripotent stem cells and mitochondrial disease modeling. Biochim Biophys Acta 1860(4):686–693

    CAS  PubMed  Google Scholar 

  28. Chen C, Tang Q, Zhang Y, Dai M, Jiang Y, Wang H, Yu M, Jing W, Tian W (2017) Metabolic reprogramming by HIF-1 activation enhances survivability of human adipose-derived stem cells in ischaemic microenvironments. Cell Prolif 50(5):e12363

    PubMed Central  Google Scholar 

  29. Oburoglu et al (2014) Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell 15(2):169–184

    CAS  PubMed  Google Scholar 

  30. Liu H, Zhang Y, Wu H, D’Alessandro A, Yegutkin GG, Song A, Sun K, Li J, Cheng NY, Huang A, Edward Wen Y, Weng TT, Luo F, Nemkov T, Sun H, Kellems RE, Karmouty-Quintana H, Hansen KC, Zhao B, Subudhi AW, Jameson-van Houten S, Julian CG, Lovering AT, Eltzschig HK, Blackburn MR, Roach RC, Xia Y (2016) Beneficial role of erythrocyte adenosine A2B receptor-mediated AMP-activated protein kinase activation in high-altitude hypoxia. Circulation 134(5):405–421

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kjaergaard J et al (2018) A 2A adenosine receptor gene deletion or synthetic A 2A antagonist liberate tumor-reactive CD8 + T cells from tumor-induced immunosuppression. J Immunol 201(2):782–791

    CAS  PubMed  Google Scholar 

  32. Carey BW et al (2014) Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518(7539):413–416

    PubMed  PubMed Central  Google Scholar 

  33. Ryall JG, Dell’Orso S, Derfoul A, Juan A, Zare H, Feng X, Clermont D, Koulnis M, Gutierrez-Cruz G, Fulco M, Sartorelli V (2015) The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells. Cell Stem Cell 16(2):171–183

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Shyhchang N et al (2013) Lin28 enhances tissue repair by reprogramming cellular metabolism. Cell 155(4):778–792

    CAS  Google Scholar 

  35. Michelet X (2018) Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol 19(12):1330–1340

    CAS  PubMed  Google Scholar 

  36. Chang CH, Curtis JD, Maggi LB Jr, Faubert B, Villarino AV, O’Sullivan D, Huang SCC, van der Windt GJW, Blagih J, Qiu J, Weber JD, Pearce EJ, Jones RG, Pearce EL (2013) Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153(6):1239–1251

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ, Nichols AG, Warmoes MO, de Cubas AA, MacIver NJ, Locasale JW, Turka LA, Wells AD, Rathmell JC (2016) Foxp3 and toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat Immunol 17(12):1459–1466

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Sica A, Strauss L (2017) Energy metabolism drives myeloid-derived suppressor cell differentiation and functions in pathology. J Leukoc Biol 102(2):325–334

    CAS  PubMed  Google Scholar 

  39. Bettencourt IA, Powell JD (2017) Targeting metabolism as a novel therapeutic approach to autoimmunity, inflammation, and transplantation. J Immunol 198(3):999

    CAS  PubMed  Google Scholar 

  40. Binger KJ, Côrtereal BF (2017) Immunometabolic Regulation of Interleukin-17-Producing T Helper Cells: Uncoupling New Targets for Autoimmunity. Front Immunol 8:311

  41. Huang L, Xu H, Peng G (2018) TLR-mediated metabolic reprogramming in the tumor microenvironment: potential novel strategies for cancer immunotherapy. Cell Mol Immunol 15:428–437

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Doherty JR, Cleveland JL (2013) Targeting lactate metabolism for cancer therapeutics. J Clin Invest 123(9):3685–3692

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, Li L, Boussiotis VA (2015) PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun 6:6692

    CAS  PubMed  Google Scholar 

  44. Noman MZ et al (2014) PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211(5):781–790

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Sun K et al (2016) Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nat Commun 7:12086

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24(24):509–581

    CAS  PubMed  Google Scholar 

  47. Knowles JR (1980) Enzyme-catalyzed phosphoryl transfer reactions. Annu Rev Biochem 49(1):877–919

    CAS  PubMed  Google Scholar 

  48. Liu H, Xia Y (2015) Beneficial and detrimental role of adenosine signaling in diseases and therapy. J Appl Physiol (1985) 119(10):1173

    CAS  Google Scholar 

  49. Mcdonough KA, Rodriguez A (2012) The myriad roles of cyclic AMP in microbial pathogens: from signal to sword. Nat Rev Microbiol 10(1):27–38

    CAS  Google Scholar 

  50. Ferrari D et al (2016) Purinergic signaling during immune cell trafficking. Trends Immunol 37(6):399–411

    CAS  PubMed  Google Scholar 

  51. Antonioli L et al (2008) Regulation of enteric functions by adenosine: pathophysiological and pharmacological implications. Pharmacol Ther 120(3):233–253

    CAS  PubMed  Google Scholar 

  52. Surprenant A, Rassendren F, Kawashima E, North RA, Buell G (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272(5262):735–738

    CAS  PubMed  Google Scholar 

  53. Adinolfi E et al (2017) The P2X7 receptor: a main player in inflammation. Biochem Pharmacol 151:S0006295217307335

    Google Scholar 

  54. Eltzschig HK (2013) Extracellular adenosine signaling in molecular medicine. J Mol Med (Berl) 91(2):141–146

    Google Scholar 

  55. Geldenhuys WJ et al (2017) Exploring adenosine receptor ligands: potential role in the treatment of cardiovascular diseases. Molecules 22(6):917

    PubMed Central  Google Scholar 

  56. Haskó G, Csóka B, Németh ZH, Vizi ES, Pacher P (2009) A2B adenosine receptors in immunity and inflammation. Trends Immunol 30(6):263–270

    PubMed  PubMed Central  Google Scholar 

  57. Abbracchio MP, Burnstock G (1994) Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther 64(3):445–475

    CAS  PubMed  Google Scholar 

  58. Jarvis MF, Khakh BS (2009) ATP-gated P2X cation-channels. Neuropharmacology 56(1):208–215

    CAS  PubMed  Google Scholar 

  59. Idzko M, Ferrari D, Eltzschig HK (2014) Nucleotide signalling during inflammation. Nature 509(7500):310–317

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Cekic C, Linden J (2016) Purinergic regulation of the immune system. Nat Rev Immunol 16(3):177–192

    CAS  PubMed  Google Scholar 

  61. Nishimura A, Sunggip C, Oda S, Numaga-Tomita T, Tsuda M, Nishida M (2017) Purinergic P2Y receptors: molecular diversity and implications for treatment of cardiovascular diseases. Pharmacol Ther 180:113–128

    CAS  PubMed  Google Scholar 

  62. Welihinda AA et al (2017) Enhancement of inosine-mediated A 2A R signaling through positive allosteric modulation. Cell Signal 42:227–235

    PubMed  PubMed Central  Google Scholar 

  63. Yarom M et al (1998) Identification of inosine as an endogenous modulator for the benzodiazepine binding site of the GABAA receptors. J Biomed Sci 5(4):274–280

    CAS  PubMed  Google Scholar 

  64. Steinberg GR, Kemp BE (2009) AMPK in health and disease. Physiol Rev 89(3):1025–1078

    CAS  PubMed  Google Scholar 

  65. Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13(4):251–262

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Kahn BB et al (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1(1):15–25

    CAS  PubMed  Google Scholar 

  67. Ricciarelli R, Fedele E (2018) cAMP, cGMP and amyloid β: three ideal partners for memory formation. Trends Neurosci 41:255–266

    CAS  PubMed  Google Scholar 

  68. Rasmussen H, Kelley G, Douglas JS (1990) Interactions between Ca2+ and cAMP messenger system in regulation of airway smooth muscle contraction. Am J Phys 258(6 Pt 1):L279

    CAS  Google Scholar 

  69. Kresge N, Simoni RD, Hill RL (2005) Earl W. Sutherland’s discovery of cyclic adenine monophosphate and the second messenger system. J Biol Chem 19(280):e39

    Google Scholar 

  70. Skalhegg BS, Tasken K (2000) Specificity in the cAMP/PKA signaling pathway. differential expression, regulation, and subcellular localization of subunits of PKA. Front Biosci 5(1):D678

    CAS  PubMed  Google Scholar 

  71. Buglioni A, Burnett JC (2016) New Pharmacological Strategies to Increase cGMP. Annu Rev Med 67:229–243

    CAS  PubMed  Google Scholar 

  72. Fan F et al (2016) Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide. Sci Rep 6:22637

    Google Scholar 

  73. Ruizgarcía A et al (2011) Cooperation of adenosine with macrophage Toll-4 receptor agonists leads to increased glycolytic flux through the enhanced expression of PFKFB3 gene. J Biol Chem 286(22):19247–19258

    Google Scholar 

  74. Hatfield SM, Sitkovsky M (2016) A2A adenosine receptor antagonists to weaken the hypoxia-HIF-1α driven immunosuppression and improve immunotherapies of cancer. Curr Opin Pharmacol 29:90–96

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Akio O et al (2012) The development and immunosuppressive functions of CD4+CD25+FoxP3+regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front Immunol 3(3):190–190

    Google Scholar 

  76. Hatfield SM et al (2015) Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med 7(277):277ra30

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Gnad T et al (2014) Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature 516(7531):395–399

    CAS  PubMed  Google Scholar 

  78. Ohta A (2016) A metabolic immune checkpoint: adenosine in tumor microenvironment. Front Immunol 7(Pt 1):109

    PubMed  PubMed Central  Google Scholar 

  79. Bantug GR, Galluzzi L, Kroemer G, Hess C (2018) The spectrum of T cell metabolism in health and disease. Nat Rev Immunol 18(1):19–34

    CAS  PubMed  Google Scholar 

  80. Burrows N, Maxwell PH (2017) Hypoxia and B cells. Exp Cell Res 356(2):197–203

    CAS  PubMed  Google Scholar 

  81. Song A, Zhang Y, Han L, Yegutkin GG, Liu H, Sun K, D’Alessandro A, Li J, Karmouty-Quintana H, Iriyama T, Weng T, Zhao S, Wang W, Wu H, Nemkov T, Subudhi AW, Jameson-van Houten S, Julian CG, Lovering AT, Hansen KC, Zhang H, Bogdanov M, Dowhan W, Jin J, Kellems RE, Eltzschig HK, Blackburn M, Roach RC, Xia Y (2017) Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent. Nat Commun 8:14108

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Liu H et al (2016) Adenosine signaling-mediated metabolic reprogramming regulates erythropoiesis. Blood :2437–2437

    Google Scholar 

  83. Palazon A et al (2014) HIF transcription factors, inflammation, and immunity. Immunity 41(4):518–528

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Stefania M et al (2005) A3 adenosine receptors modulate hypoxia-inducible factor-1alpha expression in human A375 melanoma cells. Neoplasia 7(10):894–903

    Google Scholar 

  85. Gessi S et al (2013) A 1 and a 3 adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes. Pharmacol Res 76(10):157–170

    CAS  PubMed  Google Scholar 

  86. Torres A, Erices JI, Sanchez F, Ehrenfeld P, Turchi L, Virolle T, Uribe D, Niechi I, Spichiger C, Rocha JD, Ramirez M, Salazar-Onfray F, San Martín R, Quezada C (2019) Extracellular adenosine promotes cell migration/invasion of glioblastoma stem-like cells through A3 adenosine receptor activation under hypoxia. Cancer Lett 446:112–122

    CAS  PubMed  Google Scholar 

  87. Lagory EL, Giaccia AJ (2016) The ever-expanding role of HIF in tumour and stromal biology. Nat Cell Biol 18(4):356

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Fraisl P, Aragonés J, Carmeliet P (2009) Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov 8(2):139

    CAS  PubMed  Google Scholar 

  89. Sitkovsky M, Lukashev D (2005) Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors. Nat Rev Immunol 5(9):712–721

    CAS  PubMed  Google Scholar 

  90. Xie H, Simon MC (2017) Oxygen availability and metabolic reprogramming in cancer. J Biol Chem 292(41):jbc.R117.799973

    Google Scholar 

  91. Chen CH et al (2001) Regulation of glut1 mRNA by Hypoxia-inducible Factor-1. J Biol Chem 276(12):9519–9525

    Google Scholar 

  92. Borg N, Alter C, Görldt N, Jacoby C, Ding Z, Steckel B, Quast C, Bönner F, Friebe D, Temme S, Flögel U, Schrader J (2017) CD73 on T-cells orchestrates cardiac wound healing after myocardial infarction by purinergic metabolic reprogramming. Circulation 136:297–313

    CAS  PubMed  Google Scholar 

  93. Wang X, Yang K, Xie Q, Wu Q, Mack SC, Shi Y, Kim LJY, Prager BC, Flavahan WA, Liu X, Singer M, Hubert CG, Miller TE, Zhou W, Huang Z, Fang X, Regev A, Suvà ML, Hwang TH, Locasale JW, Bao S, Rich JN (2017) Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Nat Neurosci 20(5):661–673

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Andersson O, Adams BA, Yoo D, Ellis GC, Gut P, Anderson RM, German MS, Stainier DYR (2012) Adenosine signaling promotes regeneration of pancreatic β cells in vivo. Cell Metab 15(6):885–894

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Yegutkin GG (2014) Enzymes involved in metabolism of extracellular nucleotides and nucleosides: functional implications and measurement of activities. Crit Rev Biochem Mol Biol 49(6):473–497

    CAS  PubMed  Google Scholar 

  96. Jimenez-Mateos EM, Smith J, Nicke A, Engel T (2018) Regulation of P2X7 receptor expression and function in the brain. Brain Res Bull S0361-9230(18):30734–2

  97. Liu HT, Sabirov RZ, Okada Y (2008) Oxygen-glucose deprivation induces ATP release via maxi-anion channels in astrocytes. Purinergic Signal 4(2):147–154

    CAS  PubMed  Google Scholar 

  98. Hirayama Y, Koizumi S (2017) Hypoxia-independent mechanisms of HIF-1α expression in astrocytes after ischemic preconditioning. Glia 65(3):523–530

    PubMed  Google Scholar 

  99. Lizhen L et al (2008) Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 28(3):468–481

    Google Scholar 

  100. Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, di Virgilio F (2006) The P2X7 receptor: a key player in IL-1 processing and release. J Immunol 176(7):3877–3883

    CAS  PubMed  Google Scholar 

  101. Alessandra P et al (2008) ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way. Proc Natl Acad Sci U S A 105(23):8067–8072

    Google Scholar 

  102. Ghiringhelli F, Apetoh LA (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15(10):1170–1178

    CAS  PubMed  Google Scholar 

  103. Andrea V et al (2013) Effect of the purinergic inhibitor oxidized ATP in a model of islet allograft rejection. Diabetes 62(5):1665–1675

    Google Scholar 

  104. Vergani A, Tezza S, D’Addio F, Fotino C, Liu K, Niewczas M, Bassi R, Molano RD, Kleffel S, Petrelli A, Soleti A, Ammirati E, Frigerio M, Visner G, Grassi F, Ferrero ME, Corradi D, Abdi R, Ricordi C, Sayegh MH, Pileggi A, Fiorina P (2013) Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7. Circulation 127(4):463–475

    CAS  PubMed  Google Scholar 

  105. Di VF (2013) The therapeutic potential of modifying inflammasomes and NOD-like receptors. Pharmacol Rev 65(3):872–905

    Google Scholar 

  106. Amoroso F, Capece M, Rotondo A, Cangelosi D, Ferracin M, Franceschini A, Raffaghello L, Pistoia V, Varesio L, Adinolfi E (2015) The P2X7 receptor is a key modulator of the PI3K/GSK3β/VEGF signaling network: evidence in experimental neuroblastoma. Oncogene 34(41):5240–5251

    CAS  PubMed  Google Scholar 

  107. Gómez-Villafuertes R et al (2010) Ca2+/calmodulin-dependent kinase II signalling cascade mediates P2X7 receptor-dependent inhibition of neuritogenesis in neuroblastoma cells. FEBS J 276(18):5307–5325

    Google Scholar 

  108. Beurel E, Michalek SM, Jope RS (2010) Innate and adaptive immune responses regulated by glycogen synthase kinase-3 (GSK3). Trends Immunol 31(1):24–31

    CAS  PubMed  Google Scholar 

  109. Martin M et al (2005) Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol 6(8):777–784

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Huang L, Zhang C, Su L, Song Z (2017) GSK3β attenuates TGF-β1 induced epithelial–mesenchymal transition and metabolic alterations in ARPE-19 cells. Biochem Biophys Res Commun 486(3):744–751

    CAS  PubMed  Google Scholar 

  111. Tafani M, de Santis E, Coppola L, Perrone GA, Carnevale I, Russo A, Pucci B, Carpi A, Bizzarri M, Russo MA (2014) Bridging hypoxia, inflammation and estrogen receptors in thyroid cancer progression. Biomed Pharmacother 68(1):1–5

    CAS  PubMed  Google Scholar 

  112. Henrique BDS et al (2018) The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8+ T cells. Nature 559(7713):264–268

    CAS  PubMed  Google Scholar 

  113. Adinolfi E et al (2002) P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood 99(2):706–708

    CAS  PubMed  Google Scholar 

  114. Raffaghello L, Chiozzi P, Falzoni S, di Virgilio F, Pistoia V (2006) The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. Cancer Res 66(2):907–914

    CAS  PubMed  Google Scholar 

  115. Baricordi OR, Melchiorri L, Adinolfi E, Falzoni S, Chiozzi P, Buell G, di Virgilio F (1999) Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J Biol Chem 274(47):33206–33208

    CAS  PubMed  Google Scholar 

  116. Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M, Wieckowski MR, Pinton P, Rizzuto R, di Virgilio F (2005) Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol Biol Cell 16(7):3260–3272

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Amoroso F, Falzoni S, Adinolfi E, Ferrari D, di Virgilio F (2012) The P2X7 receptor is a key modulator of aerobic glycolysis. Cell Death Differ 3(8):e370

    CAS  Google Scholar 

  118. De Marchi E et al (2019) The P2X7 receptor modulates immune cells infiltration, ectonucleotidases expression and extracellular ATP levels in the tumor microenvironment. Oncogene 38(19):3636–3650

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Sara T et al (2012) Extracellular ATP exerts opposite effects on activated and regulatory CD4+ T cells via purinergic P2 receptor activation. J Immunol 189(3):1303–1310

    Google Scholar 

  120. Di VF et al (2017) The P2X7 receptor in infection and inflammation. Immunity 47(1):15

    Google Scholar 

  121. North RA (2016) P2X receptors. Philos Trans R Soc Lond 371(1700):20150427

    Google Scholar 

  122. De ME et al (2016) P2X7 receptor as a therapeutic target. Adv Protein Chem Struct Biol 104:39

    Google Scholar 

  123. Danquah W et al (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med 8(366):366ra162

    PubMed  Google Scholar 

  124. Gilbert SM et al (2017) A phase 1 clinical trial demonstrates nfP2X 7 targeted antibodies provide a novel, safe and tolerable topical therapy for BCC. Br J Dermatol 177(1):117–124

    CAS  PubMed  Google Scholar 

  125. Laetitia A et al (2010) Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 70(3):855–858

    Google Scholar 

  126. Ma Y et al (2013) Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 38(4):729–741

    CAS  PubMed  Google Scholar 

  127. Lecciso M et al (2017) ATP release from chemotherapy-treated dying leukemia cells elicits an immune suppressive effect by increasing regulatory T cells and tolerogenic dendritic cells. Front Immunol 8:1918

    PubMed  PubMed Central  Google Scholar 

  128. Giovanna B et al (2007) Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110(4):1225–1232

    Google Scholar 

  129. Yue N et al (2017) Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors. J Neuroinflammation 14(1):102

    PubMed  PubMed Central  Google Scholar 

  130. Laskaris LE et al (2016) Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol 173(4):666–680

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Mondelli V et al (2017) Brain microglia in psychiatric disorders. Lancet Psychiatry 4(7):S2215036617301013

    Google Scholar 

  132. Kesteren CFMGV et al (2017) Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies. Transl Psychiatry 7(3):e1075

    PubMed  PubMed Central  Google Scholar 

  133. Fischer Y, Becker C, Löken C et al (1999) J Biol Chem 274(2):755–761

    CAS  PubMed  Google Scholar 

  134. Balasubramanian R et al (2014) Enhancement of glucose uptake in mouse skeletal muscle cells and adipocytes by P2Y6 receptor agonists. PLoS One 9(12):e116203–e116203

    PubMed  PubMed Central  Google Scholar 

  135. Hillairebuys D et al (1993) Stimulation of insulin secretion and improvement of glucose tolerance in rat and dog by the P2y-purinoceptor agonist, adenosine-5'-O-(2-thiodiphosphate). Br J Pharmacol 109(1):183–187

    CAS  Google Scholar 

  136. Fernandez-Alvarez J, Hillaire-Buys D, Loubatières-Mariani MM, Gomis R, Petit P (2001) P2 receptor agonists stimulate insulin release from human pancreatic islets. Pancreas 22(1):69–71

    CAS  PubMed  Google Scholar 

  137. Hardie DG (2015) AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr Opin Cell Biol 33:1–7

    CAS  PubMed  Google Scholar 

  138. Sebbagh M, Santoni MJ, Hall B, Borg JP, Schwartz MA (2009) Regulation of LKB1/STRAD localization and function by E-cadherin. Curr Biol 19(1):37–42

    CAS  PubMed  Google Scholar 

  139. Chiaranunt P, Ferrara JL, Byersdorfer CA (2015) Rethinking the paradigm: how comparative studies on fatty acid oxidation inform our understanding of T cell metabolism. Mol Immunol 68(2):564–574

    CAS  PubMed  Google Scholar 

  140. Horman S, Beauloye C, Vanoverschelde JL, Bertrand L (2012) AMP-activated protein kinase in the control of cardiac metabolism and remodeling. Curr Heart Fail Rep 9(3):164–173

    CAS  PubMed  Google Scholar 

  141. Steinberg GR, Schertzer JD (2014) AMPK promotes macrophage fatty acid oxidative metabolism to mitigate inflammation: implications for diabetes and cardiovascular disease. Immunol Cell Biol 92(4):340–345

    CAS  PubMed  Google Scholar 

  142. Mihaylova MM, Shaw RJ (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 13(9):1016–1023

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Mayer A et al (2008) AMP-activated protein kinase regulates lymphocyte responses to metabolic stress but is largely dispensable for immune cell development and function. Eur J Immunol 38(4):948–956

    CAS  PubMed  Google Scholar 

  144. Xu T, Stewart KM, Wang X, Liu K, Xie M, Ryu JK, Li K, Ma T, Wang H, Ni L, Zhu S, Cao N, Zhu D, Zhang Y, Akassoglou K, Dong C, Driggers EM, Ding S (2017) Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism. Nature 548(7666):228–233

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Luu M, Pautz S, Kohl V, Singh R, Romero R, Lucas S, Hofmann J, Raifer H, Vachharajani N, Carrascosa LC, Lamp B, Nist A, Stiewe T, Shaul Y, Adhikary T, Zaiss MM, Lauth M, Steinhoff U, Visekruna A (2019) The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes. Nat Commun 10(1):760

    PubMed  PubMed Central  Google Scholar 

  146. Julia R et al (2013) AMPKα1: a glucose sensor that controls CD8 T-cell memory. Eur J Immunol 43(4):889–896

    Google Scholar 

  147. Gj VDW et al (2012) Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36(1):68–78

    Google Scholar 

  148. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186(6):3299–3303

    CAS  PubMed  Google Scholar 

  149. Grady SL, Hwang J, Vastag L, Rabinowitz JD, Shenk T (2012) Herpes simplex virus 1 infection activates poly(ADP-ribose) polymerase and triggers the degradation of poly(ADP-ribose) Glycohydrolase. J Virol 86(15):8259–8268

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Maciver NJ et al (2011) The liver kinase B1 (LKB1) is a central regulator of T cell development, activation, and metabolism. J Immunol 187(8):4187–4198

    CAS  PubMed  Google Scholar 

  151. Angelin A, Gil-de-Gómez L, Dahiya S, Jiao J, Guo L, Levine MH, Wang Z, Quinn WJ III, Kopinski PK, Wang L, Akimova T, Liu Y, Bhatti TR, Han R, Laskin BL, Baur JA, Blair IA, Wallace DC, Hancock WW, Beier UH (2017) Foxp3 reprograms T cell metabolism to function in low-glucose, High-Lactate Environments. Cell Metab 25(6):1282–1293

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Rémi M et al (2013) AMPKα1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration. Cell Metab 18(2):251–264

    Google Scholar 

  153. Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui YC, Cui G, Micevic G, Perales JC, Kleinstein SH, Abel ED, Insogna KL, Feske S, Locasale JW, Bosenberg MW, Rathmell JC, Kaech SM (2015) Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 162(6):1217–1228

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Gualdoni GA, Mayer KA, Göschl L, Boucheron N, Ellmeier W, Zlabinger GJ (2016) The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation. FASEB J 30(11):3800–3809

    CAS  PubMed  Google Scholar 

  155. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186(6):3299–3303

    CAS  PubMed  Google Scholar 

  156. Sereni MI et al (2017) Kinase-driven metabolic signalling as a predictor of response to carboplatin-paclitaxel adjuvant treatment in advanced ovarian cancers. Br J Cancer 117(4):494–502

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Song M, Sandoval TA, Chae CS, Chopra S, Tan C, Rutkowski MR, Raundhal M, Chaurio RA, Payne KK, Konrad C, Bettigole SE, Shin HR, Crowley MJP, Cerliani JP, Kossenkov AV, Motorykin I, Zhang S, Manfredi G, Zamarin D, Holcomb K, Rodriguez PC, Rabinovich GA, Conejo-Garcia JR, Glimcher LH, Cubillos-Ruiz JR (2018) IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity. Nature 562(7727):423–428

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Schworer S, Vardhana SA, Thompson CB (2019) Cancer metabolism drives a stromal regenerative response. Cell Metab 29(3):576–591

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer D, Hwang RF, Witkiewicz AK, Ying H, Asara JM, Evans RM, Cantley LC, Lyssiotis CA, Kimmelman AC (2016) Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 536(7617):479–483

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Katheder NS, Khezri R, O’Farrell F, Schultz SW, Jain A, Rahman MM, Schink KO, Theodossiou TA, Johansen T, Juhász G, Bilder D, Brech A, Stenmark H, Rusten TE (2017) Microenvironmental autophagy promotes tumour growth. Nature 541(7637):417–420

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Yang Z et al (2017) ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway. Mol Cancer 16(1):79

    Google Scholar 

  162. Lin L, Huang H, Liao W, Ma H, Liu J, Wang L, Huang N, Liao Y, Liao W (2015) MACC1 supports human gastric cancer growth under metabolic stress by enhancing the Warburg effect. Oncogene 34(21):2700–2710

    CAS  PubMed  Google Scholar 

  163. Yang T et al (2016) MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells. Oncotarget 7(14):18085–18094

    PubMed  PubMed Central  Google Scholar 

  164. Kubben N, Misteli T (2017) Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases. Nat Rev Mol Cell Biol 18(10):595–609

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Cantó C et al (2010) Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11(3):213–219

    PubMed  PubMed Central  Google Scholar 

  166. Garciaroves PM et al (2008) Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J Biol Chem 283(51):35724–35734

    CAS  Google Scholar 

  167. Maniam S et al (2015) Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase. Cell Death Differ 22(1):156–163

    CAS  PubMed  Google Scholar 

  168. Sanchezmacedo N et al (2013) Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model. Cell Death Differ 20(4):659–668

    CAS  Google Scholar 

  169. Klingenberg M (1990) Mechanism and evolution of the uncoupling protein of brown adipose tissue. Trends Biochem Sci 15(3):108–12

    CAS  PubMed  Google Scholar 

  170. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415(6867):96–99

    CAS  PubMed  Google Scholar 

  171. Claire P et al (2008) Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. FASEB J 22(1):9–18

    Google Scholar 

  172. Alexandra K et al (2014) Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity. PLoS Genet 10(6):e1004385

    Google Scholar 

  173. Jin Z et al (2014) UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. EMBO J 30(24):4860–4873

    Google Scholar 

  174. Vozza A, Parisi G, de Leonardis F, Lasorsa FM, Castegna A, Amorese D, Marmo R, Calcagnile VM, Palmieri L, Ricquier D, Paradies E, Scarcia P, Palmieri F, Bouillaud F, Fiermonte G (2014) UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci U S A 111(3):960–965

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Zhonglin X et al (2008) Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes. Diabetes 57(12):3222–3230

    Google Scholar 

  176. Marc F et al (2005) Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 54(5):1331–1339

    Google Scholar 

  177. Pauline E et al (2014) Mitochondrial retrograde signaling mediated by UCP2 inhibits cancer cell proliferation and tumorigenesis. Cancer Res 74(14):3971–3982

    Google Scholar 

  178. Wang M et al (2017) Uncoupling protein 2 downregulation by hypoxia through repression of peroxisome proliferator-activated receptor γ promotes chemoresistance of non-small cell lung cancer. Oncotarget 8(5):8083

    PubMed  Google Scholar 

  179. Boutoual R et al (2018) Defects in the mitochondrial-tRNA modification enzymes MTO1 and GTPBP3 promote different metabolic reprogramming through a HIF-PPARγ-UCP2-AMPK axis. Sci Rep 8(1):1163

    PubMed  PubMed Central  Google Scholar 

  180. Szelechowski M et al (2018) Metabolic reprogramming in amyotrophic lateral sclerosis. Sci Rep 8(1):3953

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Daurio NA et al (2016) AMPK activation and metabolic reprogramming by tamoxifen through estrogen receptor-independent mechanisms suggests new uses for this therapeutic modality in cancer treatment. Cancer Res 76(11):3295

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Pulito C, Mori F, Sacconi A, Goeman F, Ferraiuolo M, Pasanisi P, Campagnoli C, Berrino F, Fanciulli M, Ford RJ, Levrero M, Pediconi N, Ciuffreda L, Milella M, Steinberg GR, Cioce M, Muti P, Strano S, Blandino G (2017) Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities. Cell Discov 3:17022

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Lodi A, Woods SM, Ronen SM (2014) Magnetic resonance-detectable metabolic consequences of MEK inhibition. NMR Biomed 27(6):700

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Oliveras-Ferraros C, Vazquez-Martin A, Cuyàs E, COROMINAS-FAJA B, Rodríguez-Gallego E, Fernández-Arroyo S, Martin-Castillo B, Joven J, MENENDEZ MENENDEZ J (2014) Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile. Cell Cycle 13(7):1132–1144

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Zhou X et al (2016) Metformin suppresses hypoxia-induced stabilization of HIF-1α through reprogramming of oxygen metabolism in hepatocellular carcinoma. Oncotarget 7(1):873–884

    PubMed  Google Scholar 

  186. Zarrouk M et al (2014) Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. PLoS One 9(9):e106710

    PubMed  PubMed Central  Google Scholar 

  187. Hardie DG (2007) AMP-activated protein kinase as a drug target. Annu Rev Pharmacol Toxicol 47(1):185–210

    CAS  PubMed  Google Scholar 

  188. Popovics P, Frigo DE, Schally AV, Rick FG (2015) Targeting the 5'-AMP-activated protein kinase and related metabolic pathways for the treatment of prostate cancer. Expert Opin Ther Targets 19(5):617–632

    CAS  PubMed  Google Scholar 

  189. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7117):337–342

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Gerhart-Hines Z et al (2011) The cAMP/PKA pathway rapidly activates SIRT1 to promote fatty acid oxidation independently of changes in NAD +. Mol Cell 44(6):851–863

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Maus M, Cuk M, Patel B, Lian J, Ouimet M, Kaufmann U, Yang J, Horvath R, Hornig-Do HT, Chrzanowska-Lightowlers ZM, Moore KJ, Cuervo AM, Feske S (2017) Store-operated Ca2+ entry controls induction of lipolysis and the transcriptional reprogramming to lipid metabolism. Cell Metab 25(3):698–712

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Gong KW et al (2001) cAMP-specific phosphodiesterase TbPDE1 is not essential in Trypanosoma brucei in culture or during midgut infection of tsetse flies. Mol Biochem Parasitol 116(2):229

    CAS  PubMed  Google Scholar 

  193. Cheng KK, Lee BS, Masuda T, Ito T, Ikeda K, Hirayama A, Deng L, Dong J, Shimizu K, Soga T, Tomita M, Palsson BO, Robert M (2014) Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol. Nat Commun 5(1):3233

    PubMed  Google Scholar 

  194. Lu J et al (2017) Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1. Mol Cell Endocrinol 470:105–114

    CAS  PubMed  Google Scholar 

  195. Tong T, Ryu SE, Min Y, de March CA, Bushdid C, Golebiowski J, Moon C, Park T (2017) Olfactory receptor 10J5 responding to α-cedrene regulates hepatic steatosis via the cAMP–PKA pathway. Sci Rep 7(1):9471

    PubMed  PubMed Central  Google Scholar 

  196. Nissim I et al (2014) The molecular and metabolic influence of long term agmatine consumption. J Biol Chem 289(14):9710–9729

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Carlessi R, Chen Y, Rowlands J, Cruzat VF, Keane KN, Egan L, Mamotte C, Stokes R, Gunton JE, Bittencourt PIH, Newsholme P (2017) GLP-1 receptor signalling promotes β-cell glucose metabolismviamTOR-dependent HIF-1α activation. Sci Rep 7(1):2661

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was financially supported by the grants from the Health and Family Planning Commission of Hunan Province (B20180855), Innovation Driven Planning of Central South University(2018CX028), and High-level Talent Planning of Xiangya Hospital.

Author information

Author notes

  1. Zhenwei Tang and Wenrui Ye contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhenwei Tang, Xinwei Kuang, Jia Guo, Minmin Xiang, Cong Peng, Xiang Chen & Hong Liu

  2. Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhenwei Tang, Xinwei Kuang, Jia Guo, Minmin Xiang, Cong Peng, Xiang Chen & Hong Liu

  3. Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhenwei Tang, Xinwei Kuang, Jia Guo, Minmin Xiang, Cong Peng, Xiang Chen & Hong Liu

  4. Clinical Medicine Eight-Year Program, Xiangya Medical School of Central South University, Changsha, Hunan, China

    Zhenwei Tang, Wenrui Ye & Haotian Chen

  5. Center for Molecular Metabolomics, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Hong Liu

Authors
  1. Zhenwei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenrui Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haotian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinwei Kuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Minmin Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cong Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiang Chen or Hong Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human participants and/or animals

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, Z., Ye, W., Chen, H. et al. Role of purines in regulation of metabolic reprogramming. Purinergic Signalling 15, 423–438 (2019). https://doi.org/10.1007/s11302-019-09676-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-019-09676-z

Keywords

Search

Navigation