Increased oxidative stress is associated with various diseases and aging, while adaptation to heat stress is an important determinant of survival and contributes to longevity. However, the impact of oxidative stress on heat resistance remains largely unclear. Aim: In this study we investigated how oxidative stress impinges on heat stress responses. Results: We report that hydrogen-peroxide (H2O2) pretreatment inhibits both acquired thermotolerance and heat-induced Hsp70 expression in mammalian cells, as well as acquired thermotolerance in the nematode Caenorhabditis elegans, via RNA interference. Moreover, we demonstrate that elimination of RNA interference by silencing key enzymes in microRNA biogenesis, dcr-1 or pash-1, restores the diminished intrinsic thermotolerance of aged and H2O2-elimination compromised (catalase-2 and peroxiredoxin-2 deficient) worms. Innovation and Conclusion: These results uncover a novel post-transcriptional element in the regulation of heat stress adaptation under oxidative conditions that may have implications in disease susceptibility and aging. Antioxid. Redox Signal. 17, 890–901.
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References
1.
AdachiM, LiuY, FujiiK, CalderwoodSK, NakaiA, ImaiK, ShinomuraY. Oxidative stress impairs the heat stress response and delays unfolded protein recovery. PLoS One, 4:e7719. 2009.
2.
AhnSG, ThieleDJ. Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev, 17:516–528. 2003.
3.
BackP, De VosWH, DepuydtGG, MatthijssensF, VanfleterenJR, BraeckmanBP. Exploring real-time in vivo redox biology of developing and aging Caenorhabditis elegans. Free Rad Biol Med, 52:850–859. 2012. http://dx.doi.org/10.1016/j.freeradbiomed.2011.11.0372011.
4.
Ben-ZviA, MillerEA, MorimotoRI. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci U S A, 106:14914–14919. 2009.
5.
BernsteinE, KimSY, CarmellMA, MurchisonEP, AlcornH, LiMZ, MillsAA, ElledgeSJ, AndersonKV, HannonGJ. Dicer is essential for mouse development. Nat Genet, 35:215–217. 2003.
6.
BoehmM, SlackF. A developmental timing microRNA and its target regulate life span in C. elegans. Science, 310:1954–1957. 2005.
7.
BonelliMA, AlfieriRR, PetroniniPG, BrigottiM, CampaniniC, BorghettiAF. Attenuated expression of 70-kDa heat shock protein in WI-38 human fibroblasts during aging in vitro. Exp Cell Res, 252:20–32. 1999.
8.
BrennerS. The genetics of Caenorhabditis elegans. Genetics, 77:71–94. 1974.
9.
CurrieRW, KarmazynM, KlocM, MailerK. Heat-shock response is associated with enhanced postischemic ventricular recovery. Circ Res, 63:543–549. 1988.
10.
CypserJR, JohnsonTE. Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity. J Gerontol A Biol Sci Med Sci, 57:B109–B114. 2002.
11.
de LencastreA, PincusZ, ZhouK, KatoM, LeeSS, SlackFJ. MicroRNAs both promote and antagonize longevity in C. elegans. Curr Biol, 20:2159–2168. 2010.
12.
EnyediB, VarnaiP, GeisztM. Redox state of the endoplasmic reticulum is controlled by Ero1L-alpha and intraluminal calcium. Antioxid Redox Signal, 13:721–729. 2010.
GosslauA, RuoffP, MohsenzadehS, HobohmU, RensingL. Heat shock and oxidative stress-induced exposure of hydrophobic protein domains as common signal in the induction of hsp68. J Biol Chem, 276:1814–1821. 2001.
15.
Hajdu-CroninYM, ChenWJ, SternbergPW. The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans. Genetics, 168:1937–1949. 2004.
16.
HalliwellB, GutteridgeJMC. Free Radicals in Biology and Medicine. Oxford; New York: Oxford University Press, 2007; xxxvi:851[8] p. of plates p.
17.
HuS, ClaudEC, MuschMW, ChangEB. Stress granule formation mediates the inhibition of colonic Hsp70 translation by interferon-gamma and tumor necrosis factor-alpha. Am J Physiol Gastrointest Liver Physiol, 298:G481–G492. 2010.
Ibanez-VentosoC, YangM, GuoS, RobinsH, PadgettRW, DriscollM. Modulated microRNA expression during adult lifespan in Caenorhabditis elegans. Aging Cell, 5:235–246. 2006.
20.
KimJK, GabelHW, KamathRS, TewariM, PasquinelliA, RualJF, KennedyS, DybbsM, BertinN, KaplanJM, VidalM, RuvkunG. Functional genomic analysis of RNA interference in C. elegans. Science, 308:1164–1167. 2005.
21.
KuruczI, TomborB, PrechlJ, ErdoF, HegedusE, NagyZ, VitaiM, KoranyiL, LaszloL. Ultrastructural localization of Hsp-72 examined with a new polyclonal antibody raised against the truncated variable domain of the heat shock protein. Cell Stress Chaperones, 4:139–152. 1999.
22.
LeeJS, SeoJS. Differential expression of two stress-inducible hsp70 genes by various stressors. Exp Mol Med, 34:131–136. 2002.
LiX, CassidyJJ, ReinkeCA, FischboeckS, CarthewRW. A microRNA imparts robustness against environmental fluctuation during development. Cell, 137:273–282. 2009.
25.
LinY, LiuX, ChengY, YangJ, HuoY, ZhangC. Involvement of MicroRNAs in hydrogen peroxide-mediated gene regulation and cellular injury response in vascular smooth muscle cells. J Biol Chem, 284:7903–7913. 2009.
26.
LithgowGJ, WhiteTM, MelovS, JohnsonTE. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A, 92:7540–7544. 1995.
27.
LiuQ, ParooZ. Biochemical principles of small RNA pathways. Ann Rev Biochem, 79:295–319. 2010.
28.
ManaloDJ, LinZ, LiuAY. Redox-dependent regulation of the conformation and function of human heat shock factor 1. Biochemistry, 41:2580–2588. 2002.
29.
McCollG, RogersAN, AlavezS, HubbardAE, MelovS, LinkCD, BushAI, KapahiP, LithgowGJ. Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab, 12:260–272.
30.
McMillanDR, XiaoX, ShaoL, GravesK, BenjaminIJ. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem, 273:7523–7528. 1998.
31.
MiskaEA, Alvarez-SaavedraE, AbbottAL, LauNC, HellmanAB, McGonagleSM, BartelDP, AmbrosVR, HorvitzHR. Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability. PLoS Genet, 3:e215. 2007.
32.
MorimotoRI. Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev, 22:1427–1438. 2008.
33.
MoseleyPL, WallenES, McCaffertyJD, FlanaganS, KernJA. Heat stress regulates the human 70-kDa heat-shock gene through the 3'-untranslated region. Am J Physiol, 264:L533–L537. 1993.
34.
MullerFL, LustgartenMS, JangY, RichardsonA, Van RemmenH. Trends in oxidative aging theories. Free Radic Biol Med, 43:477–503. 2007.
35.
NambaT, TanakaK, HoshinoT, AzumaA, MizushimaT. Suppression of expression of heat shock protein 70 by gefitinib and its contribution to pulmonary fibrosis. PLoS ONE, 6:e27296. 2011.
36.
OberringerM, BaumHP, JungV, WelterC, FrankJ, KuhlmannM, MutschlerW, HanselmannRG. Differential expression of heat shock protein 70 in well healing and chronic human wound tissue. Biochem Biophys Res Commun, 214:1009–1014. 1995.
37.
OlahovaM, TaylorSR, KhazaipoulS, WangJ, MorganBA, MatsumotoK, BlackwellTK, VealEA. A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Proc Natl Acad Sci U S A, 105:19839–19844. 2008.
38.
PetersenRB, LindquistS. Regulation of HSP70 synthesis by messenger RNA degradation. Cell Regul, 1:135–149. 1989.
39.
PetrivOI, RachubinskiRA. Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. J Biol Chem, 279:19996–20001. 2004.
40.
PuticsA, VeghEM, CsermelyP, SotiC. Resveratrol induces the heat-shock response and protects human cells from severe heat stress. Antioxid Redox Signal, 10:65–75. 2008.
41.
RehwinkelJ, NatalinP, StarkA, BrenneckeJ, CohenSM, IzaurraldeE. Genome-wide analysis of mRNAs regulated by Drosha and Argonaute proteins in Drosophila melanogaster. Mol Cell Biol, 26:2965–2975. 2006.
SteelsEL, WatsonK, ParsonsPG. Relationships between thermotolerance, oxidative stress responses and induction of stress proteins in human tumour cell lines. Biochem Pharmacol, 44:2123–2129. 1992.
TimmonsL, CourtDL, FireA. Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene, 263:103–112. 2001.
46.
TranterM, HelsleyRN, PauldingWR, McGuinnessM, BrokampC, HaarL, LiuY, RenX, JonesWK. Coordinated post-transcriptional regulation of Hsp70.3 gene expression by microRNA and alternative polyadenylation. J Biol Chem, 286:29828–29837. 2011.
47.
WalkerGA, LithgowGJ. Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell, 2:131–139. 2003.
48.
YinC, SalloumFN, KukrejaRC. A novel role of microRNA in late preconditioning: upregulation of endothelial nitric oxide synthase and heat shock protein 70. Circ Res, 104:572–575. 2009.
49.
YinC, WangX, KukrejaRC. Endogenous microRNAs induced by heat-shock reduce myocardial infarction following ischemia-reperfusion in mice. FEBS Lett, 582:4137–4142. 2008.
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