Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Feb;91(2):465–473. doi: 10.1172/JCI116224

Vascular heat shock protein expression in response to stress. Endocrine and autonomic regulation of this age-dependent response.

R Udelsman 1, M J Blake 1, C A Stagg 1, D G Li 1, D J Putney 1, N J Holbrook 1
PMCID: PMC287957  PMID: 8094399

Abstract

Adaptation to stress requires coordinated interactions between the vascular and endocrine systems. Previously we demonstrated that restraint stress induces the expression of the major heat shock protein, HSP70, in the adrenal cortex of the rat. Here we demonstrate that restraint also induces expression of HSP70 in the vasculature. We further demonstrate that the adrenal and vascular responses are differentially regulated: the adrenal response is adrenocorticotropin dependent, whereas the vascular response is under adrenergic control. In addition, the adrenal response is restricted to members of the HSP70 gene family, whereas in vascular tissue the low molecular weight HSP, HSP27, is also induced by restraint. Further characterization of the vascular response revealed that HSP70 induction occurred in both the thoracic and abdominal aortas as well as in the vena cava. However, no HSP70 induction was apparent in the heart or in a wide variety of other tissues examined. In situ hybridization showed that the vascular expression was localized to the aortic smooth muscle cells with minimal expression in the endothelium. Induction of HSP70 mRNA in both the adrenal cortex and aorta was followed by an elevation in HSP70 protein. Maximum HSP70 protein levels were seen within 3-12 h after restraint, but declined thereafter. Stress induced HSP70 expression was dramatically reduced with age, which may explain, in part, the diminished tolerance to stress seen in elderly individuals.

Full text

PDF
465

Images in this article

467Image
on p.467
467Image
on p.467
468Image
on p.468
468Image
on p.468
468Image
on p.468
469Image
on p.469
470Image
on p.470
470Image
on p.470
471Image
on p.471

Selected References

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

  1. Anderson R. L., Van Kersen I., Kraft P. E., Hahn G. M. Biochemical analysis of heat-resistant mouse tumor cell strains: a new member of the HSP70 family. Mol Cell Biol. 1989 Aug;9(8):3509–3516. doi: 10.1128/mcb.9.8.3509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ang D., Liberek K., Skowyra D., Zylicz M., Georgopoulos C. Biological role and regulation of the universally conserved heat shock proteins. J Biol Chem. 1991 Dec 25;266(36):24233–24236. [PubMed] [Google Scholar]
  3. Angelidis C. E., Lazaridis I., Pagoulatos G. N. Constitutive expression of heat-shock protein 70 in mammalian cells confers thermoresistance. Eur J Biochem. 1991 Jul 1;199(1):35–39. doi: 10.1111/j.1432-1033.1991.tb16088.x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Berberian P. A., Myers W., Tytell M., Challa V., Bond M. G. Immunohistochemical localization of heat shock protein-70 in normal-appearing and atherosclerotic specimens of human arteries. Am J Pathol. 1990 Jan;136(1):71–80. [PMC free article] [PubMed] [Google Scholar]
  6. Berberian P. A., Myers W., Tytell M., Challa V., Bond M. G. Immunohistochemical localization of heat shock protein-70 in normal-appearing and atherosclerotic specimens of human arteries. Am J Pathol. 1990 Jan;136(1):71–80. [PMC free article] [PubMed] [Google Scholar]
  7. Bitar K. N., Kaminski M. S., Hailat N., Cease K. B., Strahler J. R. Hsp27 is a mediator of sustained smooth muscle contraction in response to bombesin. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1192–1200. doi: 10.1016/0006-291x(91)92065-r. [DOI] [PubMed] [Google Scholar]
  8. Blake M. J., Nowak T. S., Jr, Holbrook N. J. In vivo hyperthermia induces expression of HSP70 mRNA in brain regions controlling the neuroendocrine response to stress. Brain Res Mol Brain Res. 1990 Jun;8(1):89–92. doi: 10.1016/0169-328x(90)90014-5. [DOI] [PubMed] [Google Scholar]
  9. Blake M. J., Udelsman R., Feulner G. J., Norton D. D., Holbrook N. J. Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9873–9877. doi: 10.1073/pnas.88.21.9873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carper S. W., Duffy J. J., Gerner E. W. Heat shock proteins in thermotolerance and other cellular processes. Cancer Res. 1987 Oct 15;47(20):5249–5255. [PubMed] [Google Scholar]
  11. Choi H. S., Lin Z., Li B. S., Liu A. Y. Age-dependent decrease in the heat-inducible DNA sequence-specific binding activity in human diploid fibroblasts. J Biol Chem. 1990 Oct 15;265(29):18005–18011. [PubMed] [Google Scholar]
  12. Chrétien P., Landry J. Enhanced constitutive expression of the 27-kDa heat shock proteins in heat-resistant variants from Chinese hamster cells. J Cell Physiol. 1988 Oct;137(1):157–166. doi: 10.1002/jcp.1041370119. [DOI] [PubMed] [Google Scholar]
  13. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Currie R. W., White F. P. Trauma-induced protein in rat tissues: a physiological role for a "heat shock" protein? Science. 1981 Oct 2;214(4516):72–73. doi: 10.1126/science.7280681. [DOI] [PubMed] [Google Scholar]
  15. Fargnoli J., Kunisada T., Fornace A. J., Jr, Schneider E. L., Holbrook N. J. Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. Proc Natl Acad Sci U S A. 1990 Jan;87(2):846–850. doi: 10.1073/pnas.87.2.846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gething M. J., Sambrook J. Protein folding in the cell. Nature. 1992 Jan 2;355(6355):33–45. doi: 10.1038/355033a0. [DOI] [PubMed] [Google Scholar]
  17. Giuffre K. A., Udelsman R., Listwak S., Chrousos G. P. Effects of immune neutralization of corticotropin-releasing hormone, adrenocorticotropin, and beta-endorphin in the surgically stressed rat. Endocrinology. 1988 Jan;122(1):306–310. doi: 10.1210/endo-122-1-306. [DOI] [PubMed] [Google Scholar]
  18. Gower D. J., Hollman C., Lee K. S., Tytell M. Spinal cord injury and the stress protein response. J Neurosurg. 1989 Apr;70(4):605–611. doi: 10.3171/jns.1989.70.4.0605. [DOI] [PubMed] [Google Scholar]
  19. Heufelder A. E., Goellner J. R., Wenzel B. E., Bahn R. S. Immunohistochemical detection and localization of a 72-kilodalton heat shock protein in autoimmune thyroid disease. J Clin Endocrinol Metab. 1992 Apr;74(4):724–731. doi: 10.1210/jcem.74.4.1548334. [DOI] [PubMed] [Google Scholar]
  20. Hunt C., Morimoto R. I. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6455–6459. doi: 10.1073/pnas.82.19.6455. [DOI] [PMC free article] [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. Jurivich D. A., Sistonen L., Kroes R. A., Morimoto R. I. Effect of sodium salicylate on the human heat shock response. Science. 1992 Mar 6;255(5049):1243–1245. doi: 10.1126/science.1546322. [DOI] [PubMed] [Google Scholar]
  23. Knowlton A. A., Brecher P., Apstein C. S. Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. J Clin Invest. 1991 Jan;87(1):139–147. doi: 10.1172/JCI114963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Landry J., Chrétien P., Lambert H., Hickey E., Weber L. A. Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells. J Cell Biol. 1989 Jul;109(1):7–15. doi: 10.1083/jcb.109.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Laszlo A., Li G. C. Heat-resistant variants of Chinese hamster fibroblasts altered in expression of heat shock protein. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8029–8033. doi: 10.1073/pnas.82.23.8029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Li G. C., Li L. G., Liu Y. K., Mak J. Y., Chen L. L., Lee W. M. Thermal response of rat fibroblasts stably transfected with the human 70-kDa heat shock protein-encoding gene. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1681–1685. doi: 10.1073/pnas.88.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  29. Liu A. Y., Lin Z., Choi H. S., Sorhage F., Li B. Attenuated induction of heat shock gene expression in aging diploid fibroblasts. J Biol Chem. 1989 Jul 15;264(20):12037–12045. [PubMed] [Google Scholar]
  30. Minota S., Cameron B., Welch W. J., Winfield J. B. Autoantibodies to the constitutive 73-kD member of the hsp70 family of heat shock proteins in systemic lupus erythematosus. J Exp Med. 1988 Oct 1;168(4):1475–1480. doi: 10.1084/jem.168.4.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Munck A., Guyre P. M., Holbrook N. J. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984 Winter;5(1):25–44. doi: 10.1210/edrv-5-1-25. [DOI] [PubMed] [Google Scholar]
  32. Pavlov E. P., Harman S. M., Chrousos G. P., Loriaux D. L., Blackman M. R. Responses of plasma adrenocorticotropin, cortisol, and dehydroepiandrosterone to ovine corticotropin-releasing hormone in healthy aging men. J Clin Endocrinol Metab. 1986 Apr;62(4):767–772. doi: 10.1210/jcem-62-4-767. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Sapolsky R. M., Krey L. C., McEwen B. S. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev. 1986 Aug;7(3):284–301. doi: 10.1210/edrv-7-3-284. [DOI] [PubMed] [Google Scholar]
  35. Sorger P. K., Lewis M. J., Pelham H. R. Heat shock factor is regulated differently in yeast and HeLa cells. Nature. 1987 Sep 3;329(6134):81–84. doi: 10.1038/329081a0. [DOI] [PubMed] [Google Scholar]
  36. Sorger P. K., Pelham H. R. Cloning and expression of a gene encoding hsc73, the major hsp70-like protein in unstressed rat cells. EMBO J. 1987 Apr;6(4):993–998. doi: 10.1002/j.1460-2075.1987.tb04850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Udelsman R., Blake M. J., Holbrook N. J. Molecular response to surgical stress: specific and simultaneous heat shock protein induction in the adrenal cortex, aorta, and vena cava. Surgery. 1991 Dec;110(6):1125–1131. [PubMed] [Google Scholar]
  38. Udelsman R., Harwood J. P., Millan M. A., Chrousos G. P., Goldstein D. S., Zimlichman R., Catt K. J., Aguilera G. Functional corticotropin releasing factor receptors in the primate peripheral sympathetic nervous system. Nature. 1986 Jan 9;319(6049):147–150. doi: 10.1038/319147a0. [DOI] [PubMed] [Google Scholar]
  39. Udelsman R., Ramp J., Gallucci W. T., Gordon A., Lipford E., Norton J. A., Loriaux D. L., Chrousos G. P. Adaptation during surgical stress. A reevaluation of the role of glucocorticoids. J Clin Invest. 1986 Apr;77(4):1377–1381. doi: 10.1172/JCI112443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Uney J. B., Leigh P. N., Marsden C. D., Lees A., Anderton B. H. Stereotaxic injection of kainic acid into the striatum of rats induces synthesis of mRNA for heat shock protein 70. FEBS Lett. 1988 Aug 1;235(1-2):215–218. doi: 10.1016/0014-5793(88)81265-1. [DOI] [PubMed] [Google Scholar]
  41. Vass K., Welch W. J., Nowak T. S., Jr Localization of 70-kDa stress protein induction in gerbil brain after ischemia. Acta Neuropathol. 1988;77(2):128–135. doi: 10.1007/BF00687422. [DOI] [PubMed] [Google Scholar]
  42. Welch W. J., Suhan J. P. Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J Cell Biol. 1986 Nov;103(5):2035–2052. doi: 10.1083/jcb.103.5.2035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wu B. J., Kingston R. E., Morimoto R. I. Human HSP70 promoter contains at least two distinct regulatory domains. Proc Natl Acad Sci U S A. 1986 Feb;83(3):629–633. doi: 10.1073/pnas.83.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yamamori T., Yura T. Genetic control of heat-shock protein synthesis and its bearing on growth and thermal resistance in Escherichia coli K-12. Proc Natl Acad Sci U S A. 1982 Feb;79(3):860–864. doi: 10.1073/pnas.79.3.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yost H. J., Lindquist S. RNA splicing is interrupted by heat shock and is rescued by heat shock protein synthesis. Cell. 1986 Apr 25;45(2):185–193. doi: 10.1016/0092-8674(86)90382-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES