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. 1996 Jun 25;93(13):6458–6463. doi: 10.1073/pnas.93.13.6458

Mitochondria are selective targets for the protective effects of heat shock against oxidative injury.

B S Polla 1, S Kantengwa 1, D François 1, S Salvioli 1, C Franceschi 1, C Marsac 1, A Cossarizza 1
PMCID: PMC39045  PMID: 8692837

Abstract

Heat shock (HS) proteins (HSPs) induce protection against a number of stresses distinct from HS, including reactive oxygen species. In the human premonocytic line U937, we investigated in whole cells the effects of preexposure to HS and exposure to hydrogen peroxide (H2O2) on mitochondrial membrane potential, mass, and ultrastructure. HS prevented H2O2-induced alterations in mitochondrial membrane potential and cristae formation while increasing expression of HSPs and the protein product of bcl-2. Protection correlated best with the expression of the 70-kDa HSP, hsp70. We propose that mitochondria represent a selective target for HS-mediated protection against oxidative injury.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barbe M. F., Tytell M., Gower D. J., Welch W. J. Hyperthermia protects against light damage in the rat retina. Science. 1988 Sep 30;241(4874):1817–1820. doi: 10.1126/science.3175623. [DOI] [PubMed] [Google Scholar]
  2. Borkan S. C., Emami A., Schwartz J. H. Heat stress protein-associated cytoprotection of inner medullary collecting duct cells from rat kidney. Am J Physiol. 1993 Sep;265(3 Pt 2):F333–F341. doi: 10.1152/ajprenal.1993.265.3.F333. [DOI] [PubMed] [Google Scholar]
  3. Cleary M. L., Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. doi: 10.1073/pnas.82.21.7439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
  5. Clerget M., Polla B. S. Erythrophagocytosis induces heat shock protein synthesis by human monocytes-macrophages. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1081–1085. doi: 10.1073/pnas.87.3.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cossarizza A., Baccarani-Contri M., Kalashnikova G., Franceschi C. A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun. 1993 Nov 30;197(1):40–45. doi: 10.1006/bbrc.1993.2438. [DOI] [PubMed] [Google Scholar]
  7. Cossarizza A., Ceccarelli D., Masini A. Functional heterogeneity of an isolated mitochondrial population revealed by cytofluorometric analysis at the single organelle level. Exp Cell Res. 1996 Jan 10;222(1):84–94. doi: 10.1006/excr.1996.0011. [DOI] [PubMed] [Google Scholar]
  8. Cossarizza A., Cooper E. L., Quaglino D., Salvioli S., Kalachnikova G., Franceschi C. Mitochondrial mass and membrane potential in coelomocytes from the earthworm Eisenia foetida: studies with fluorescent probes in single intact cells. Biochem Biophys Res Commun. 1995 Sep 14;214(2):503–510. doi: 10.1006/bbrc.1995.2315. [DOI] [PubMed] [Google Scholar]
  9. Cossarizza A., Kalashnikova G., Grassilli E., Chiappelli F., Salvioli S., Capri M., Barbieri D., Troiano L., Monti D., Franceschi C. Mitochondrial modifications during rat thymocyte apoptosis: a study at the single cell level. Exp Cell Res. 1994 Sep;214(1):323–330. doi: 10.1006/excr.1994.1264. [DOI] [PubMed] [Google Scholar]
  10. Currie R. W., Karmazyn M., Kloc M., Mailer K. Heat-shock response is associated with enhanced postischemic ventricular recovery. Circ Res. 1988 Sep;63(3):543–549. doi: 10.1161/01.res.63.3.543. [DOI] [PubMed] [Google Scholar]
  11. Delia D., Aiello A., Soligo D., Fontanella E., Melani C., Pezzella F., Pierotti M. A., Della Porta G. bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells. Blood. 1992 Mar 1;79(5):1291–1298. [PubMed] [Google Scholar]
  12. Donati Y. R., Slosman D. O., Polla B. S. Oxidative injury and the heat shock response. Biochem Pharmacol. 1990 Dec 15;40(12):2571–2577. doi: 10.1016/0006-2952(90)90573-4. [DOI] [PubMed] [Google Scholar]
  13. Driggers W. J., LeDoux S. P., Wilson G. L. Repair of oxidative damage within the mitochondrial DNA of RINr 38 cells. J Biol Chem. 1993 Oct 15;268(29):22042–22045. [PubMed] [Google Scholar]
  14. Feige U., Polla B. S. Hsp70--a multi-gene, multi-structure, multi-function family with potential clinical applications. Experientia. 1994 Nov 30;50(11-12):979–986. doi: 10.1007/BF01923452. [DOI] [PubMed] [Google Scholar]
  15. Gabai V. L., Kabakov A. E. Rise in heat-shock protein level confers tolerance to energy deprivation. FEBS Lett. 1993 Aug 2;327(3):247–250. doi: 10.1016/0014-5793(93)80997-9. [DOI] [PubMed] [Google Scholar]
  16. Halliwell B. Oxidants and human disease: some new concepts. FASEB J. 1987 Nov;1(5):358–364. [PubMed] [Google Scholar]
  17. Hennet T., Richter C., Peterhans E. Tumour necrosis factor-alpha induces superoxide anion generation in mitochondria of L929 cells. Biochem J. 1993 Jan 15;289(Pt 2):587–592. doi: 10.1042/bj2890587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hockenbery D. M., Oltvai Z. N., Yin X. M., Milliman C. L., Korsmeyer S. J. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993 Oct 22;75(2):241–251. doi: 10.1016/0092-8674(93)80066-n. [DOI] [PubMed] [Google Scholar]
  19. Jacquier-Sarlin M. R., Fuller K., Dinh-Xuan A. T., Richard M. J., Polla B. S. Protective effects of hsp70 in inflammation. Experientia. 1994 Nov 30;50(11-12):1031–1038. doi: 10.1007/BF01923458. [DOI] [PubMed] [Google Scholar]
  20. Jacquier-Sarlin M. R., Jornot L., Polla B. S. Differential expression and regulation of hsp70 and hsp90 by phorbol esters and heat shock. J Biol Chem. 1995 Jun 9;270(23):14094–14099. doi: 10.1074/jbc.270.23.14094. [DOI] [PubMed] [Google Scholar]
  21. Johnston R. N., Kucey B. L. Competitive inhibition of hsp70 gene expression causes thermosensitivity. Science. 1988 Dec 16;242(4885):1551–1554. doi: 10.1126/science.3201244. [DOI] [PubMed] [Google Scholar]
  22. Jättelä M. Overexpression of major heat shock protein hsp70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J Immunol. 1993 Oct 15;151(8):4286–4294. [PubMed] [Google Scholar]
  23. Kane D. J., Sarafian T. A., Anton R., Hahn H., Gralla E. B., Valentine J. S., Ord T., Bredesen D. E. Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science. 1993 Nov 19;262(5137):1274–1277. doi: 10.1126/science.8235659. [DOI] [PubMed] [Google Scholar]
  24. Kantengwa S., Capponi A. M., Bonventre J. V., Polla B. S. Calcium and the heat-shock response in the human monocytic line U-937. Am J Physiol. 1990 Jul;259(1 Pt 1):C77–C83. doi: 10.1152/ajpcell.1990.259.1.C77. [DOI] [PubMed] [Google Scholar]
  25. Karmazyn M. The 1990 Merck Frosst Award. Ischemic and reperfusion injury in the heart. Cellular mechanisms and pharmacological interventions. Can J Physiol Pharmacol. 1991 Jun;69(6):719–730. doi: 10.1139/y91-108. [DOI] [PubMed] [Google Scholar]
  26. Mailhos C., Howard M. K., Latchman D. S. Heat shock protects neuronal cells from programmed cell death by apoptosis. Neuroscience. 1993 Aug;55(3):621–627. doi: 10.1016/0306-4522(93)90428-i. [DOI] [PubMed] [Google Scholar]
  27. Maridonneau-Parini I., Malawista S. E., Stubbe H., Russo-Marie F., Polla B. S. Heat shock in human neutrophils: superoxide generation is inhibited by a mechanism distinct from heat-denaturation of NADPH oxidase and is protected by heat shock proteins in thermotolerant cells. J Cell Physiol. 1993 Jul;156(1):204–211. doi: 10.1002/jcp.1041560127. [DOI] [PubMed] [Google Scholar]
  28. Mariéthoz E., Tacchini-Cottier F., Jacquier-Sarlin M., Sinclair F., Polla B. S. Exposure of monocytes to heat shock does not increase class II expression but modulates antigen-dependent T cell responses. Int Immunol. 1994 Jun;6(6):925–930. doi: 10.1093/intimm/6.6.925. [DOI] [PubMed] [Google Scholar]
  29. Mehlen P., Preville X., Chareyron P., Briolay J., Klemenz R., Arrigo A. P. Constitutive expression of human hsp27, Drosophila hsp27, or human alpha B-crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol. 1995 Jan 1;154(1):363–374. [PubMed] [Google Scholar]
  30. Minisini M. P., Kantengwa S., Polla B. S. DNA damage and stress protein synthesis induced by oxidative stress proceed independently in the human premonocytic line U937. Mutat Res. 1994 Sep;315(2):169–179. doi: 10.1016/0921-8777(94)90016-7. [DOI] [PubMed] [Google Scholar]
  31. Mosser D. D., Martin L. H. Induced thermotolerance to apoptosis in a human T lymphocyte cell line. J Cell Physiol. 1992 Jun;151(3):561–570. doi: 10.1002/jcp.1041510316. [DOI] [PubMed] [Google Scholar]
  32. Pace G. W., Leaf C. D. The role of oxidative stress in HIV disease. Free Radic Biol Med. 1995 Oct;19(4):523–528. doi: 10.1016/0891-5849(95)00047-2. [DOI] [PubMed] [Google Scholar]
  33. Patriarca E. J., Maresca B. Acquired thermotolerance following heat shock protein synthesis prevents impairment of mitochondrial ATPase activity at elevated temperatures in Saccharomyces cerevisiae. Exp Cell Res. 1990 Sep;190(1):57–64. doi: 10.1016/0014-4827(90)90143-x. [DOI] [PubMed] [Google Scholar]
  34. Petit J. M., Maftah A., Ratinaud M. H., Julien R. 10N-nonyl acridine orange interacts with cardiolipin and allows the quantification of this phospholipid in isolated mitochondria. Eur J Biochem. 1992 Oct 1;209(1):267–273. doi: 10.1111/j.1432-1033.1992.tb17285.x. [DOI] [PubMed] [Google Scholar]
  35. Plumier J. C., Ross B. M., Currie R. W., Angelidis C. E., Kazlaris H., Kollias G., Pagoulatos G. N. Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. J Clin Invest. 1995 Apr;95(4):1854–1860. doi: 10.1172/JCI117865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Polla B. S., Bonventre J. V., Krane S. M. 1,25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide in the human monocytic line U937: the role of calcium and heat shock. J Cell Biol. 1988 Jul;107(1):373–380. doi: 10.1083/jcb.107.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Polla B. S., Healy A. M., Amento E. P., Krane S. M. 1,25-Dihydroxyvitamin D3 maintains adherence of human monocytes and protects them from thermal injury. J Clin Invest. 1986 Apr;77(4):1332–1339. doi: 10.1172/JCI112438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Polla B. S., Stubbe H., Kantengwa S., Maridonneau-Parini I., Jacquier-Sarlin M. R. Differential induction of stress proteins and functional effects of heat shock in human phagocytes. Inflammation. 1995 Jun;19(3):363–378. doi: 10.1007/BF01534393. [DOI] [PubMed] [Google Scholar]
  39. Reers M., Smith T. W., Chen L. B. J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential. Biochemistry. 1991 May 7;30(18):4480–4486. doi: 10.1021/bi00232a015. [DOI] [PubMed] [Google Scholar]
  40. Riabowol K. T., Mizzen L. A., Welch W. J. Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. Science. 1988 Oct 21;242(4877):433–436. doi: 10.1126/science.3175665. [DOI] [PubMed] [Google Scholar]
  41. Richter C., Kass G. E. Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis, cell death, proliferation, and differentiation. Chem Biol Interact. 1991;77(1):1–23. doi: 10.1016/0009-2797(91)90002-o. [DOI] [PubMed] [Google Scholar]
  42. Schmid I., Schmid P., Giorgi J. V. Conversion of logarithmic channel numbers into relative linear fluorescence intensity. Cytometry. 1988 Nov;9(6):533–538. doi: 10.1002/cyto.990090605. [DOI] [PubMed] [Google Scholar]
  43. Sharif M., Worrall J. G., Singh B., Gupta R. S., Lydyard P. M., Lambert C., McCulloch J., Rook G. A. The development of monoclonal antibodies to the human mitochondrial 60-kd heat-shock protein, and their use in studying the expression of the protein in rheumatoid arthritis. Arthritis Rheum. 1992 Dec;35(12):1427–1433. doi: 10.1002/art.1780351205. [DOI] [PubMed] [Google Scholar]
  44. Smiley S. T., Reers M., Mottola-Hartshorn C., Lin M., Chen A., Smith T. W., Steele G. D., Jr, Chen L. B. Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3671–3675. doi: 10.1073/pnas.88.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Spurr A. R. A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res. 1969 Jan;26(1):31–43. doi: 10.1016/s0022-5320(69)90033-1. [DOI] [PubMed] [Google Scholar]
  46. Stuart R. A., Cyr D. M., Neupert W. Hsp70 in mitochondrial biogenesis: from chaperoning nascent polypeptide chains to facilitation of protein degradation. Experientia. 1994 Nov 30;50(11-12):1002–1011. doi: 10.1007/BF01923454. [DOI] [PubMed] [Google Scholar]
  47. Villar J., Ribeiro S. P., Mullen J. B., Kuliszewski M., Post M., Slutsky A. S. Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model. Crit Care Med. 1994 Jun;22(6):914–921. [PubMed] [Google Scholar]

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