Abstract
Oxidative stress is one of the major and continuous stresses, an organism encounters during its lifetime. Tissues such as the brain, liver and muscles are more prone to damage by oxidative stress due to their metabolic activity, differences in physiological and adaptive processes. One of the defence mechanisms against continuous oxidative stress is a set of small heat shock proteins. αB-Crystallin/HSPB5, a small heat shock protein, gets upregulated under stress and acts as a molecular chaperone. In addition to acting as a molecular chaperone, HSPB5 is shown to have a role in other cytoprotective functions such as inhibition of apoptosis, prevention of oxidative stress and stabilisation of cytoskeletal system. Such protection in vivo, at the organism level, particularly in a tissue-dependent manner, has not been investigated. We have expressed HSPB5 in fat body (liver), neurons and specifically in dopaminergic and motor neurons in Drosophila and investigated its protective effect against paraquat-induced oxidative stress. We observed that expression of HSPB5 in neurons and fat body confers protection against paraquat-induced oxidative stress. Expression in dopaminergic neurons showed a higher protective effect. Our results clearly establish the protective ability of HSPB5 in vivo; the extent of protection, however, varies depending on the tissue in which it is expressed. Interestingly, neuronal expression of HSPB5 resulted in an improvement in negative geotropic behaviour, whereas specific expression in muscle tissue did not show such a beneficial effect.
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Abbreviations
- HSP:
-
Heat shock protein
- sHsp:
-
Small heat shock protein
- NTD:
-
N-terminal domain
- ACD:
-
Alpha crystallin domain
- CTE:
-
C-terminal extension
- ALS:
-
Amyotrophic lateral sclerosis
References
Adhikari AS, Singh BN, Rao KS, Rao Ch M (2011) alphaB-Crystallin, a small heat shock protein, modulates NF-kappaB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-alpha induced cytotoxicity. Biochim Biophys Acta 1813:1532–1542. https://doi.org/10.1016/j.bbamcr.2011.04.009
Ahmad MF, Singh D, Taiyab A, Ramakrishna T, Raman B, Rao Ch M (2008) Selective Cu2+ binding, redox silencing, and cytoprotective effects of the small heat shock proteins alphaA- and alphaB-crystallin. J Mol Biol 382:812–824. https://doi.org/10.1016/j.jmb.2008.07.068
Bailey SM, Cunningham CC (1998) Acute and chronic ethanol increases reactive oxygen species generation and decreases viability in fresh, isolated rat hepatocytes. Hepatology 28:1318–1326. https://doi.org/10.1002/hep.510280521
Berry C, La Vecchia C, Nicotera P (2010) Paraquat and Parkinson’s disease. Cell Death Differ 17:1115–1125. https://doi.org/10.1038/cdd.2009.217
Bhat SP, Nagineni CN (1989) alpha B Subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. Biochem Biophys Res Commun 158:319–325. https://doi.org/10.1016/s0006-291x(89)80215-3
Bosoi CR, Yang X, Huynh J, Parent-Robitaille C, Jiang W, Tremblay M, Rose CF (2012) Systemic oxidative stress is implicated in the pathogenesis of brain edema in rats with chronic liver failure. Free Radic Biol Med 52:1228–1235. https://doi.org/10.1016/j.freeradbiomed.2012.01.006
Bradford BU et al (2005) Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver. Hepatology 41:336–344. https://doi.org/10.1002/hep.20532
Bus JS, Gibson JE (1984) Paraquat: model for oxidant-initiated toxicity. Environ Health Perspect 55:37–46. https://doi.org/10.1289/ehp.845537
Cassiman D et al (2001) Alpha B-crystallin expression in human and rat hepatic stellate cells. J Hepatol 35:200–207. https://doi.org/10.1016/s0168-8278(01)00122-2
Chaudhuri A, Bowling K, Funderburk C, Lawal H, Inamdar A, Wang Z, O’Donnell JM (2007) Interaction of genetic and environmental factors in a Drosophila parkinsonism model. J Neurosci 27:2457–2467. https://doi.org/10.1523/JNEUROSCI.4239-06.2007
Chen S, Brown IR (2007) Neuronal expression of constitutive heat shock proteins: implications for neurodegenerative diseases. Cell Stress Chaperones 12:51–58. https://doi.org/10.1379/csc-236r.1
Chis R, Sharma P, Bousette N, Miyake T, Wilson A, Backx PH, Gramolini AO (2012) alpha-Crystallin B prevents apoptosis after H2O2 exposure in mouse neonatal cardiomyocytes. Am J Physiol Heart Circ Physiol 303:H967–H978. https://doi.org/10.1152/ajpheart.00040.2012
Cobley JN, Fiorello ML, Bailey DM (2018) 13 reasons why the brain is susceptible to oxidative stress. Redox Biol 15:490–503. https://doi.org/10.1016/j.redox.2018.01.008
Cookson MR, Shaw PJ (1999) Oxidative stress and motor neurone disease. Brain Pathol 9:165–186. https://doi.org/10.1111/j.1750-3639.1999.tb00217.x
Cui H, Kong Y, Zhang H (2012) Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012:646354. https://doi.org/10.1155/2012/646354
de Jong WW, Leunissen JA, Voorter CE (1993) Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol 10:103–126. https://doi.org/10.1093/oxfordjournals.molbev.a039992
Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 3:461–491. https://doi.org/10.3233/JPD-130230
Franck E, Madsen O, van Rheede T, Ricard G, Huynen MA, de Jong WW (2004) Evolutionary diversity of vertebrate small heat shock proteins. J Mol Evol 59:792–805. https://doi.org/10.1007/s00239-004-0013-z
Friedman J (2011) Why is the nervous system vulnerable to oxidative stress? :19-27. https://doi.org/10.1007/978-1-60327-514-9_2
Fukushima T, Tanaka K, Lim H, Moriyama M (2002) Mechanism of cytotoxicity of paraquat. Environ Health Prev Med 7:89–94. https://doi.org/10.1265/ehpm.2002.89
Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ, Partridge L (2004) Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 305:361. https://doi.org/10.1126/science.1098219
Groenen PJ, Merck KB, de Jong WW, Bloemendal H (1994) Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology. Eur J Biochem 225:1–19. https://doi.org/10.1111/j.1432-1033.1994.00001.x
Guo JD, Zhao X, Li Y, Li GR, Liu XL (2018) Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease (Review). Int J Mol Med 41:1817–1825. https://doi.org/10.3892/ijmm.2018.3406
Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623. https://doi.org/10.1111/j.1471-4159.1992.tb10990.x
Hart TB (1987) Paraquat--a review of safety in agricultural and horticultural use. Hum Toxicol 6:13–18. https://doi.org/10.1177/096032718700600103
Hatcher JM, Pennell KD, Miller GW (2008) Parkinson’s disease and pesticides: a toxicological perspective. Trends Pharmacol Sci 29:322–329. https://doi.org/10.1016/j.tips.2008.03.007
Higuchi H, Adachi M, Miura S, Gores GJ, Ishii H (2001) The mitochondrial permeability transition contributes to acute ethanol-induced apoptosis in rat hepatocytes. Hepatology 34:320–328. https://doi.org/10.1053/jhep.2001.26380
Horwitz J (1992) Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci U S A 89:10449–10453. https://doi.org/10.1073/pnas.89.21.10449
Ingolia TD, Craig EA (1982) Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin. Proc Natl Acad Sci U S A 79:2360–2364. https://doi.org/10.1073/pnas.79.7.2360
Iwaki T, Kume-Iwaki A, Goldman JE (1990) Cellular distribution of alpha B-crystallin in non-lenticular tissues. J Histochem Cytochem 38:31–39. https://doi.org/10.1177/38.1.2294148
Jenner P, Dexter DT, Sian J, Schapira AH, Marsden CD (1992) Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson’s Disease Research Group. Ann Neurol 32(Suppl):S82–S87. https://doi.org/10.1002/ana.410320714
Kamradt MC, Chen F, Cryns VL (2001) The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J Biol Chem 276:16059–16063. https://doi.org/10.1074/jbc.C100107200
Kappe G, Franck E, Verschuure P, Boelens WC, Leunissen JA, de Jong WW (2003) The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones 8:53–61. https://doi.org/10.1379/1466-1268(2003)8<53:thgecs>2.0.co;2
Kriehuber T, Rattei T, Weinmaier T, Bepperling A, Haslbeck M, Buchner J (2010) Independent evolution of the core domain and its flanking sequences in small heat shock proteins. FASEB J 24:3633–3642. https://doi.org/10.1096/fj.10-156992
Kukielka E, Dicker E, Cederbaum AI (1994) Increased production of reactive oxygen species by rat liver mitochondria after chronic ethanol treatment. Arch Biochem Biophys 309:377–386. https://doi.org/10.1006/abbi.1994.1127
Lang A et al (2000) Expression of small heat shock protein alphaB-crystallin is induced after hepatic stellate cell activation. Am J Physiol Gastrointest Liver Physiol 279:G1333–G1342. https://doi.org/10.1152/ajpgi.2000.279.6.G1333
Lee FY, Kast-Woelbern HR, Chang J, Luo G, Jones SA, Fishbein MC, Edwards PA (2005) Alpha-crystallin is a target gene of the farnesoid X-activated receptor in human livers. J Biol Chem 280:31792–31800. https://doi.org/10.1074/jbc.M503182200
Leeuwenburgh C, Hollander J, Leichtweis S, Griffiths M, Gore M, Ji LL (1997) Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. Am J Phys 272:R363–R369. https://doi.org/10.1152/ajpregu.1997.272.1.R363
Liguori I et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513
Maatkamp A, Vlug A, Haasdijk E, Troost D, French PJ, Jaarsma D (2004) Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS-SOD1 mice. Eur J Neurosci 20:14–28. https://doi.org/10.1111/j.1460-9568.2004.03430.x
Mandrekar P, Szabo G (2009) Signalling pathways in alcohol-induced liver inflammation. J Hepatol 50:1258–1266. https://doi.org/10.1016/j.jhep.2009.03.007
Masarone M, Rosato V, Dallio M, Gravina AG, Aglitti A, Loguercio C, Federico A, Persico M (2018) Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease. Oxidative Med Cell Longev 2018:9547613. https://doi.org/10.1155/2018/9547613
Masilamoni JG, Jesudason EP, Bharathi SN, Jayakumar R (2005) The protective effect of alpha-crystallin against acute inflammation in mice. Biochim Biophys Acta 1740:411–420. https://doi.org/10.1016/j.bbadis.2004.11.002
McGreal RS, Kantorow WL, Chauss DC, Wei J, Brennan LA, Kantorow M (2012) alphaB-Crystallin/sHSP protects cytochrome c and mitochondrial function against oxidative stress in lens and retinal cells. Biochim Biophys Acta 1820:921–930. https://doi.org/10.1016/j.bbagen.2012.04.004
Michaud S, Morrow G, Marchand J, Tanguay RM (2002) Drosophila small heat shock proteins: cell and organelle-specific chaperones? Prog Mol Subcell Biol 28:79–101. https://doi.org/10.1007/978-3-642-56348-5_5
Morrow G, Samson M, Michaud S, Tanguay RM (2004) Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J 18:598–599. https://doi.org/10.1096/fj.03-0860fje
Muriel P (2009) Role of free radicals in liver diseases. Hepatol Int 3:526–536. https://doi.org/10.1007/s12072-009-9158-6
Musselman LP et al (2013) Role of fat body lipogenesis in protection against the effects of caloric overload in Drosophila. J Biol Chem 288:8028–8042. https://doi.org/10.1074/jbc.M112.371047
Musselman LP, Kuhnlein RP (2018) Drosophila as a model to study obesity and metabolic disease. J Exp Biol 221:jeb163881. https://doi.org/10.1242/jeb.163881
Mutlu-Turkoglu U, Dogru-Abbasoglu S, Aykac-Toker G, Mirsal H, Beyazyurek M, Uysal M (2000) Increased lipid and protein oxidation and DNA damage in patients with chronic alcoholism. J Lab Clin Med 136:287–291. https://doi.org/10.1067/mlc.2000.109097
Owusu-Ansah E, Perrimon N (2014) Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases. Dis Model Mech 7:343–350. https://doi.org/10.1242/dmm.012989
Parola M, Robino G (2001) Oxidative stress-related molecules and liver fibrosis. J Hepatol 35:297–306. https://doi.org/10.1016/s0168-8278(01)00142-8
Perng MD, Muchowski PJ, van Den IP, Wu GJ, Hutcheson AM, Clark JI, Quinlan RA (1999) The cardiomyopathy and lens cataract mutation in alphaB-crystallin alters its protein structure, chaperone activity, and interaction with intermediate filaments in vitro. J Biol Chem 274:33235–33243. https://doi.org/10.1074/jbc.274.47.33235
Pham-Huy LA, He H, Pham-Huy C (2008) Free radicals, antioxidants in disease and health. Int J Biomed Sci 4:89–96
Raman B, Rao CM (1994) Chaperone-like activity and quaternary structure of alpha-crystallin. J Biol Chem 269:27264–27268
Reiter LT, Potocki L, Chien S, Gribskov M, Bier E (2001) A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res 11:1114–1125. https://doi.org/10.1101/gr.169101
Robertson HM, Preston CR, Phillis RW, Johnson-Schlitz DM, Benz WK, Engels WR (1988) A stable genomic source of P element transposase in Drosophila melanogaster. Genetics 118:461–470
Rogers RS, Beaudoin MS, Wheatley JL, Wright DC, Geiger PC (2015) Heat shock proteins: in vivo heat treatments reveal adipose tissue depot-specific effects. J Appl Physiol (1985) 118:98–106. https://doi.org/10.1152/japplphysiol.00286.2014
Rzezniczak TZ, Douglas LA, Watterson JH, Merritt TJ (2011) Paraquat administration in Drosophila for use in metabolic studies of oxidative stress. Anal Biochem 419:345–347. https://doi.org/10.1016/j.ab.2011.08.023
Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K (2011) Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet 26:30–46. https://doi.org/10.2133/dmpk.dmpk-10-rv-087
Shin JH, Kim SW, Lim CM, Jeong JY, Piao CS, Lee JK (2009) alphaB-crystallin suppresses oxidative stress-induced astrocyte apoptosis by inhibiting caspase-3 activation. Neurosci Res 64:355–361. https://doi.org/10.1016/j.neures.2009.04.006
Singh BN, Rao KS, Ramakrishna T, Rangaraj N, Rao Ch M (2007) Association of alphaB-crystallin, a small heat shock protein, with actin: role in modulating actin filament dynamics in vivo. J Mol Biol 366:756–767. https://doi.org/10.1016/j.jmb.2006.12.012
Sondergaard L (1993) Homology between the mammalian liver and the Drosophila fat body. Trends Genet 9:193. https://doi.org/10.1016/0168-9525(93)90113-v
Surai PF, Noble RC, Speake BK (1996) Tissue-specific differences in antioxidant distribution and susceptibility to lipid peroxidation during development of the chick embryo. Biochim Biophys Acta 1304:1–10. https://doi.org/10.1016/s0005-2760(96)00099-9
Tanguay R, Morrow G (2008) Neural expression of small heat shock proteins influences longevity and resistance to oxidative stress. In pp 319–336. https://doi.org/10.1007/978-1-4020-8231-3_16
Vidali M, Stewart SF, Albano E (2008) Interplay between oxidative stress and immunity in the progression of alcohol-mediated liver injury. Trends Mol Med 14:63–71. https://doi.org/10.1016/j.molmed.2007.12.005
Wang HD, Kazemi-Esfarjani P, Benzer S (2004) Multiple-stress analysis for isolation of Drosophila longevity genes. Proc Natl Acad Sci U S A 101:12610–12615. https://doi.org/10.1073/pnas.0404648101
Wang X, Michaelis EK (2010) Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci 2:12. https://doi.org/10.3389/fnagi.2010.00012
Webb C, Twedt D (2008) Oxidative stress and liver disease. Vet Clin North Am Small Anim Pract 38:125–135. https://doi.org/10.1016/j.cvsm.2007.10.001
Wojtowicz I et al (2015) Drosophila small heat shock protein CryAB ensures structural integrity of developing muscles, and proper muscle and heart performance. Development 142:994–1005. https://doi.org/10.1242/dev.115352
Xie J et al (2014) Differential expression of heat shock transcription factors and heat shock proteins after acute and chronic heat stress in laying chickens (Gallus gallus). PLoS One 9:e102204. https://doi.org/10.1371/journal.pone.0102204
Acknowledgements
We thank Dr. Rakesh Kumar Mishra for his help with the fly experiments. We thank Dr. T. Ramakrishna Murti for critical reading of the manuscript.
Funding
CMR is a recipient of Sir JC Bose National Fellowship of the SERB, DST (Government of India). PB is a recipient of the Council of Scientific and Industrial Research, New Delhi, senior research fellowship.
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Budnar, P., Singh, N.P. & Rao, C.M. HSPB5 (αB-crystallin) confers protection against paraquat-induced oxidative stress at the organismal level in a tissue-dependent manner. Cell Stress and Chaperones 26, 229–239 (2021). https://doi.org/10.1007/s12192-020-01171-4
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DOI: https://doi.org/10.1007/s12192-020-01171-4