Skip to main content

Advertisement

SpringerLink
Log in

Molecular characterization and functional analysis of apoptosis-inducing factor (AIF) in palmitic acid-induced apoptosis in Ctenopharyngodon idellus kidney (CIK) cells

  • Published:
Fish Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Palmitic acid (PA), the most common saturated free fatty acid, may cause apoptosis when overloaded in non-fat cells. Apoptosis-inducing factor (AIF) is known to translocate from the mitochondria into the nucleus to induce apoptosis. However, it remains to be investigated whether AIF involved in palmitic acid-induced lipoapoptosis in fish. In the present study, we cloned a coding sequence of grass carp (Ctenopharyngodon idella) AIF (CiAIF) gene, and determined its function in Ctenopharyngodon idellus kidney (CIK) cells. The open reading frame (ORF) of CiAIF gene is 1863 bp, encoding a precursor protein of 620 amino acids (aa). Sequence analysis indicated that CiAIF contains a mitochondrial localization sequence, a conserved Pyr_redox and a C-terminal domain. Phylogenetic analyses showed that the CiAIF gene tended to cluster with sequences from Danio rerio. CiAIF gene was ubiquitously expressed in all tested tissues, including heart, liver, spleen, muscle, brain, eye, kidney, intestine, and fat. Moreover, we demonstrated that PA treatment induced the expression level of CiAIF and increases in markers of endoplasmic reticulum (ER) stress and apoptosis. Meanwhile, ER stress-inducing agent thapsigargin (TG) induced CiAIF translocated into the nucleus in CIK cells, whereas the suppression of ER stress inhibited PA-induced CiAIF expression and apoptosis. In addition, overexpression of CiAIF caused apoptosis by upregulating capase9, capase8, and capase3b, and affects protein translation via directly interacting with CieIF3g. Taken together, our data indicate that in Ctenopharyngodon idellus, PA is key elements that affect not only ER stress and mitochondrial apoptosis but also different physiological functions, such as protein translation, and CiAIF might play a key role in this progress.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

Data and materials are available upon request.

References

  • Arabi YM, Tamimi W, Jones G, Jawdat D, Tamim H, Al-Dorzi HM, Sadat M, Afesh L, Sakhija M, Al-Dawood A (2019) Free fatty acids’ level and nutrition in critically ill patients and association with outcomes: a prospective sub-study of PermiT trial. Nutrients. 11:384

    Article  CAS  Google Scholar 

  • Cnop M, Foufelle F, Velloso LA (2012) Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med 18(1):59–68

    Article  CAS  Google Scholar 

  • Desmots F, Russell HR, Michel D, McKinnon PJ (2008) Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum stress-induced apoptosis. J Biol Chem 283(6):3264–3271

    Article  CAS  Google Scholar 

  • Gomes-Duarte A, Lacerda R, Menezes J, Romao L (2018) eIF3: a factor for human health and disease. RNA Biol 15(1):26–34

    Article  Google Scholar 

  • Grootjans J, Kaser A, Kaufman RJ, Blumberg RS (2016) The unfolded protein response in immunity and inflammation. Nat Rev Immunol 16(8):469–484

    Article  CAS  Google Scholar 

  • Guida M, Zanon A, Montibeller L, Lavdas AA, Ladurner J, Pischedda F, Rakovic A, Domingues FS, Piccoli G, Klein C, Pramstaller PP, Hicks AA, Pichler I (2019) Parkin interacts with apoptosis-inducing factor and interferes with its translocation to the nucleus in neuronal cells. Int J Mol Sci 20(3):748

    Article  CAS  Google Scholar 

  • Han J, Back SH, Hur J, Lin YH, Gildersleeve R, Shan J, Yuan CL, Krokowski D, Wang S, Hatzoglou M, Kilberg MS, Sartor MA, Kaufman RJ (2013) ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol 15(5):481–490

    Article  CAS  Google Scholar 

  • Hangen E, Feraud O, Lachkar S, Mou H, Doti N, Fimia GM, Lam NV, Zhu C, Godin I, Muller K, Chatzi A, Nuebel E, Ciccosanti F, Flamant S, Benit P, Perfettini JL, Sauvat A, Bennaceur-Griscelli A, Ser-Le Roux K, Gonin P, Tokatlidis K, Rustin P, Piacentini M, Ruvo M, Blomgren K, Kroemer G, Modjtahedi N (2015) Interaction between AIF and CHCHD4 regulates respiratory chain biogenesis. Mol Cell 58(6):1001–1014

    Article  CAS  Google Scholar 

  • Heath-Engel HM, Chang NC, Shore GC (2008) The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene. 27(50):6419–6433

    Article  CAS  Google Scholar 

  • Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 140(6):900–917

    Article  CAS  Google Scholar 

  • Hu WY, Yao CL (2016) Molecular and immune response characterizations of a novel AIF and cytochrome c in Litopenaeus vannamei defending against WSSV infection. Fish Shellfish Immunol 56:84–95

    Article  CAS  Google Scholar 

  • Jia SN, Lin C, Chen DF, Li AQ, Dai L, Zhang L, Zhao LL, Yang JS, Yang F, Yang WJ (2016) The transcription factor p8 regulates autophagy in response to palmitic acid stress via a mammalian target of rapamycin (mTOR)-independent signaling pathway. J Biol Chem 291(9):4462–4472

    Article  CAS  Google Scholar 

  • Jiang XS, Chen XM, Wan JM, Gui HB, Ruan XZ, Du XG (2017) Autophagy protects against palmitic acid-induced apoptosis in podocytes in vitro. Sci Rep 7:42764

    Article  CAS  Google Scholar 

  • Jin X, Riew TR, Kim HL, Kim S, Lee MY (2018) Spatiotemporal expression of GRP78 in the blood vessels of rats treated with 3-nitropropionic acid correlates with blood-brain barrier disruption. Front Cell Neurosci 12:434

    Article  CAS  Google Scholar 

  • Joza N, Galindo K, Pospisilik JA, Benit P, Rangachari M, Kanitz EE, Nakashima Y, Neely GG, Rustin P, Abrams JM, Kroemer G, Penninger JM (2008) The molecular archaeology of a mitochondrial death effector: AIF in Drosophila. Cell Death Differ 15(6):1009–1018

    Article  CAS  Google Scholar 

  • Kim JT, Kim KD, Song EY, Lee HG, Kim JW, Kim JW, Chae SK, Kim E, Lee MS, Yang Y, Lim JS (2006) Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g). FEBS Lett 580(27):6375–6383

    Article  CAS  Google Scholar 

  • Lu RH, Chang ZG, Sun J, Yang F, Nie GX, Ji H (2016) Molecular cloning, expression and functional characterization of tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein (TRIP) in grass carp, Ctenopharyngodon idella. Fish Shellfish Immunol 57:406–412

    Article  CAS  Google Scholar 

  • Otera H, Ohsakaya S, Nagaura Z, Ishihara N, Mihara K (2005) Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space. EMBO J 24(7):1375–1386

    Article  CAS  Google Scholar 

  • Papackova Z, Cahova M (2015) Fatty acid signaling: the new function of intracellular lipases. Int J Mol Sci 16(2):3831–3855

    Article  CAS  Google Scholar 

  • Polster BM, Basanez G, Etxebarria A, Hardwick JM, Nicholls DG (2005) Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem 280(8):6447–6454

    Article  CAS  Google Scholar 

  • Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jaattela M, Penninger JM, Garrido C, Kroemer G (2001) Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol 3(9):839–843

    Article  CAS  Google Scholar 

  • Sevrioukova IF (2011) Apoptosis-inducing factor: structure, function, and redox regulation. Antioxid Redox Signal 14(12):2545–2579

    Article  CAS  Google Scholar 

  • Shore GC, Papa FR, Oakes SA (2011) Signaling cell death from the endoplasmic reticulum stress response. Curr Opin Cell Biol 23(2):143–149

    Article  CAS  Google Scholar 

  • Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 397(6718):441–446

    Article  CAS  Google Scholar 

  • Takahara I, Akazawa Y, Tabuchi M, Matsuda K, Miyaaki H, Kido Y, Kanda Y, Taura N, Ohnita K, Takeshima F, Sakai Y, Eguchi S, Nakashima M, Nakao K (2017) Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice. PLoS One 12(3):e0170591

    Article  Google Scholar 

  • Vahsen N, Cande C, Briere JJ, Benit P, Joza N, Larochette N, Mastroberardino PG, Pequignot MO, Casares N, Lazar V, Feraud O, Debili N, Wissing S, Engelhardt S, Madeo F, Piacentini M, Penninger JM, Schagger H, Rustin P, Kroemer G (2004) AIF deficiency compromises oxidative phosphorylation. EMBO J 23(23):4679–4689

    Article  CAS  Google Scholar 

  • Wang D, Liang J, Zhang Y, Gui B, Wang F, Yi X, Sun L, Yao Z, Shang Y (2012) Steroid receptor coactivator-interacting protein (SIP) inhibits caspase-independent apoptosis by preventing apoptosis-inducing factor (AIF) from being released from mitochondria. J Biol Chem 287(16):12612–12621

    Article  CAS  Google Scholar 

  • Win S, Than TA, Le BH, Garcia-Ruiz C, Fernandez-Checa JC, Kaplowitz N (2015) Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity. J Hepatol 62(6):1367–1374

    Article  CAS  Google Scholar 

  • Wu KM, Hsu YM, Ying MC, Tsai FJ, Tsai CH, Chung JG, Yang JS, Tang CH, Cheng LY, Su PH, Viswanadha VP, Kuo WW, Huang CY (2019) High-density lipoprotein ameliorates palmitic acid-induced lipotoxicity and oxidative dysfunction in H9c2 cardiomyoblast cells via ROS suppression. Nutr Metab 16:36

    Article  Google Scholar 

  • Yu G, Luo H, Zhang N, Wang Y, Li Y, Huang H, Liu Y, Hu Y, Liu H, Zhang J, Tang Y, Huang Y (2019) Loss of p53 sensitizes cells to palmitic acid-induced apoptosis by reactive oxygen species accumulation. Int J Mol Sci 20(24):6268

    Article  CAS  Google Scholar 

  • Zhang F, Zhang R, Zhang X, Wu Y, Li X, Zhang S, Hou W, Ding Y, Tian J, Sun L, Kong X (2018a) Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits. Aging. 10(9):2266–2283

    Article  CAS  Google Scholar 

  • Zhang Y, Miao L, Zhang H, Wu G, Zhang Z, Lv J (2018b) Chlorogenic acid against palmitic acid in endoplasmic reticulum stress-mediated apoptosis resulting in protective effect of primary rat hepatocytes. Lipids Health Dis 17(1):270

    Article  CAS  Google Scholar 

Download references

Funding

This work was financially supported by the National Nature Science Foundation of China (NSFC, Grant Number: 31772863 and 32072989).

Author information

Authors and Affiliations

  1. College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi Province, China

    Zhiguang Chang, Minghui Yang & Hong Ji

Authors
  1. Zhiguang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Minghui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Zhiguang Chang and Minghui Yang designed and performed the experiments; Zhiguang Chang wrote the manuscript; Minghui Yang collected the literature; Hong Ji primarily revised the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Hong Ji.

Ethics declarations

Competing interests

The authors declare that they have no conflict of interest. All the authors listed have approved to submit to your journal.

Ethics declarations

All procedures were performed in accordance with the Guide for Care and Use of Laboratory Animals and approved by the Northwest A&F University Institutional Animal Care and Use Committee.

Additional information

Publisher’s note

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

Supplementary Information

ESM 1

(PDF 372 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chang, Z., Yang, M. & Ji, H. Molecular characterization and functional analysis of apoptosis-inducing factor (AIF) in palmitic acid-induced apoptosis in Ctenopharyngodon idellus kidney (CIK) cells. Fish Physiol Biochem 47, 213–224 (2021). https://doi.org/10.1007/s10695-020-00907-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10695-020-00907-4

Keywords

Search

Navigation