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Gene Review

Hspd1  -  heat shock protein 1 (chaperonin)

Rattus norvegicus

Synonyms: 60 kDa chaperonin, 60 kDa heat shock protein, mitochondrial, CPN60, Chaperonin 60, HSP-60, ...
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Disease relevance of Hspd1

  • These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy [1].
  • The independent effect of insulin and hyperglycemia on Hsp60 was investigated in primary cardiomyocytes [2].
  • Hsp10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroEs is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E. coli homologue of mycobacterial hsp65 [3].
  • In the present study we report the occurrence of chaperonins, cpn10 and cpn60, in Chromatium vinosum and rat hepatocytes, using specific polyclonal antibodies in conjunction with the protein A-gold immunocytochemical technique [4].
  • Therefore, in contrast to the accepted concept that cross-reactive T cell recognition of foreign and self antigens might induce aggressive autoimmune disease, we propose that cross-reactivity between bacterial and self hsp60 might also be used to maintain a protective self-reactive T cell population [5].

Psychiatry related information on Hspd1

  • Examination of antibodies raised against HSP65 showed no overt differences in plasma levels following chronic alcohol consumption, and liver changes as assessed by histology were mild [6].

High impact information on Hspd1

  • Moreover, arthritic rats in the late phase of AA also raised vigorous T cell responses to those carboxy-terminal determinants within self(rat) hsp65 (Rhsp65) that correspond in position to the above BCTD [7].
  • Hsp65 shares 48% amino acid identity with mammalian hsp60, which is expressed at elevated levels in inflamed synovia [5].
  • We previously described nine major histocompatibility complex class II-restricted epitopes in mycobacterial hsp65 recognized by Lewis rat T cells [5].
  • Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A [8].
  • Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats [9].

Chemical compound and disease context of Hspd1

  • Because phlorizin does not alter insulin secretion, Hsp60 expression was modulated by insulin and not by hyperglycemia [2].
  • NCM were infected with adenoviral vectors expressing mPHGPx, cPHGPx, HSP60/10, or an empty control (Adv-) and submitted to 8 h of ischemia followed by 16 h of reoxygenation. mPHGPx infection led to a 40% decrease in malondialdehyde and 4-hydroxy-2(E)-nonenal following I/R (p<.05) [10].
  • In Sprague-Dawley rats maintained under propofol anaesthesia, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg(-1)) [11].
  • 4. The effect of maleate may be partially non-specific and involve a great variety of proteins, but seems to be restricted to selected tissues because alpha 1 subunit Na+,K(+)-ATPase and hsp60 protein amounts were not significantly modified in livers from rats developing Fanconi syndrome [12].
  • However the effects of caerulein, melatonin or hyperthermia preconditioning on mRNA signal for HSP60 in the pancreatic acinar cells has not been examined yet [13].

Biological context of Hspd1


Anatomical context of Hspd1


Associations of Hspd1 with chemical compounds

  • In contrast, the abundance of Hsp60 was not affected by high concentration of glucose in these cells [2].
  • In the phlorizin-treated diabetic rats, myocardial Hsp60 was lower than that of the normal controls [2].
  • In the streptozotocin (STZ)-induced diabetic rat, downregulation of Hsp60 and IGF-1 receptor occurred 4 days after induction of diabetes [2].
  • Antisense Hsp60 reduced the abundance of endogenous Hsp60 in cardiomyocytes and amplified the cytotoxicity of doxorubicin [15].
  • Thus, like the bacterial homologue, mitochondrial cpn10 facilitates a K(+)- and Mg.ATP-dependent discharge of unfolded (or partially folded) ribulose bisphosphate carboxylase from bacterial chaperonin 60 (cpn60; also known as groEL) [16].

Physical interactions of Hspd1


Regulatory relationships of Hspd1

  • Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope [19].
  • We conclude that HSP60 redistributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxaemia via reduced activation of the cytochrome c-caspase-3 cascade of apoptotic signalling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl-2 [11].
  • We demonstrated that water-immersion stress or TRH administration specifically induced HSP60, although preinduction of this protein did not show a cytoprotective function in the small intestinal mucosa [20].
  • Moreover, feeding Hsp65/SBTI resulted in a lower number of both spleen and mesenteric lymph node (MLN) cells expressing the costimulatory molecule CD80 (B7-1) [21].
  • Our findings suggest the presence of mycobacterial hsp65 determinants that selectively trigger AA-regulating T cells and illustrate that cathepsin D may be used as an experimental tool to generate such determinants [22].

Other interactions of Hspd1

  • Bacterial and mitochondrial cpn10 compete for a common saturable site on bacterial cpn60 [16].
  • A comparison of steady-state levels of mitochondrial enzyme activity [cytochrome c oxidase (CYTOX)] with chaperonin levels [the heat-shock protein HSP60, the glucose-regulated protein GRP75 (mtHSP70)] in striated muscles possessing a wide range of oxidative capacities revealed a proportional expression between the two [23].
  • In primary cultures and brain tissue, the increased Hsp70 mRNA levels were still more than 500-fold less than constitutive Hsc70 mRNA and 50-fold less than Hsp60 levels [24].
  • In summary, endothelial cells stressed by high temperature or certain cytokines, eg, TNF-alpha, express hsp60 in the cytoplasm and on their surfaces, and these cells were susceptible to complement-dependent lysis by hsp60-specific antibody [25].
  • These results indicate that overexpression of PHGPx provides protection against damage resulting from simulated I/R injury, particularly in the mitochondria, and that the combination of mPHGPx and HSP60/10 imparts an added protective effect [10].

Analytical, diagnostic and therapeutic context of Hspd1


  1. Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. Shan, Y.X., Yang, T.L., Mestril, R., Wang, P.H. J. Biol. Chem. (2003) [Pubmed]
  2. Insulin deficiency downregulated heat shock protein 60 and IGF-1 receptor signaling in diabetic myocardium. Chen, H.S., Shan, Y.X., Yang, T.L., Lin, H.D., Chen, J.W., Lin, S.J., Wang, P.H. Diabetes (2005) [Pubmed]
  3. A synthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis. Ragno, S., Winrow, V.R., Mascagni, P., Lucietto, P., Di Pierro, F., Morris, C.J., Blake, D.R. Clin. Exp. Immunol. (1996) [Pubmed]
  4. Presence of Chromatium vinosum chaperonins 10 and 60 in mitochondria and peroxisomes of rat hepatocytes. Vélez-Granell, C.S., Arias, A.E., Torres-Ruíz, J.A., Bendayan, M. Biol. Cell (1995) [Pubmed]
  5. Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis. Anderton, S.M., van der Zee, R., Prakken, B., Noordzij, A., van Eden, W. J. Exp. Med. (1995) [Pubmed]
  6. Protein profiling in cardiac tissue in response to the chronic effects of alcohol. Patel, V.B., Corbett, J.M., Dunn, M.J., Winrow, V.R., Portmann, B., Richardson, P.J., Preedy, V.R. Electrophoresis (1997) [Pubmed]
  7. Diversification of T cell responses to carboxy-terminal determinants within the 65-kD heat-shock protein is involved in regulation of autoimmune arthritis. Moudgil, K.D., Chang, T.T., Eradat, H., Chen, A.M., Gupta, R.S., Brahn, E., Sercarz, E.E. J. Exp. Med. (1997) [Pubmed]
  8. T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins. Mor, F., Cohen, I.R. J. Clin. Invest. (1992) [Pubmed]
  9. Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats. Lee, H.S., Bhagat, L., Frossard, J.L., Hietaranta, A., Singh, V.P., Steer, M.L., Saluja, A.K. Gastroenterology (2000) [Pubmed]
  10. Overexpression of PHGPx and HSP60/10 protects against ischemia/reoxygenation injury. Hollander, J.M., Lin, K.M., Scott, B.T., Dillmann, W.H. Free Radic. Biol. Med. (2003) [Pubmed]
  11. Heat shock protein 60 in rostral ventrolateral medulla reduces cardiovascular fatality during endotoxaemia in the rat. Chang, A.Y., Chan, J.Y., Chou, J.L., Li, F.C., Dai, K.Y., Chan, S.H. J. Physiol. (Lond.) (2006) [Pubmed]
  12. Na+,K(+)-ATPase expression in maleic-acid-induced Fanconi syndrome in rats. Castaño, E., Marzabal, P., Casado, F.J., Felipe, A., Pastor-Anglada, M. Clin. Sci. (1997) [Pubmed]
  13. Increase of heat shock protein gene expression by melatonin in AR42J cells. Bonior, J., Jaworek, J., Konturek, S.J., Pawlik, W.W. J. Physiol. Pharmacol. (2005) [Pubmed]
  14. Nucleotide sequence of rat hsp60 (chaperonin, GroEL homolog) cDNA. Venner, T.J., Gupta, R.S. Nucleic Acids Res. (1990) [Pubmed]
  15. Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells. Shan, Y.X., Liu, T.J., Su, H.F., Samsamshariat, A., Mestril, R., Wang, P.H. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  16. Identification of a groES-like chaperonin in mitochondria that facilitates protein folding. Lubben, T.H., Gatenby, A.A., Donaldson, G.K., Lorimer, G.H., Viitanen, P.V. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  17. Methylprednisolone-induced expression of mitochondrial heat shock protein 60 protects mitochondrial membrane potential in the hypoxic rat liver. Motoyama, S., Saito, S., Itoh, H., Minamiya, Y., Maruyama, K., Okuyama, M., Ogawa, J. Shock (2004) [Pubmed]
  18. Molecular chaperones in pancreatic tissue: the presence of cpn10, cpn60 and hsp70 in distinct compartments along the secretory pathway of the acinar cells. Vélez-Granell, C.S., Arias, A.E., Torres-Ruíz, J.A., Bendayan, M. J. Cell. Sci. (1994) [Pubmed]
  19. Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope. Prakken, B.J., Roord, S., van Kooten, P.J., Wagenaar, J.P., van Eden, W., Albani, S., Wauben, M.H. Arthritis Rheum. (2002) [Pubmed]
  20. Effect of preinduction of heat-shock proteins on acetic acid-induced small intestinal lesions in rats. Sasahara, H., Otaka, M., Itoh, S., Iwabuchi, A., Odashima, M., Wada, I., Konishi, N., Pacheco, I.I., Tashima, Y., Itoh, H., Otani, S., Masamune, O. Dig. Dis. Sci. (1998) [Pubmed]
  21. Treatment of adjuvant-induced arthritis by oral administration of mycobacterial Hsp65 during disease. Cobelens, P.M., Heijnen, C.J., Nieuwenhuis, E.E., Kramer, P.P., van der Zee, R., van Eden, W., Kavelaars, A. Arthritis Rheum. (2000) [Pubmed]
  22. Differential rat T cell recognition of cathepsin D-released fragments of mycobacterial 65 kDa heat-shock protein after immunization with either the recombinant protein or whole mycobacteria. van Noort, J.M., Anderton, S.M., Wagenaar, J.P., Wauben, M.H., van Holten, C., Boog, C.J. Int. Immunol. (1994) [Pubmed]
  23. Expression of stress proteins and mitochondrial chaperonins in chronically stimulated skeletal muscle. Ornatsky, O.I., Connor, M.K., Hood, D.A. Biochem. J. (1995) [Pubmed]
  24. Changes in mRNA levels for heat-shock/stress proteins (Hsp) and a secretory vesicle associated cysteine-string protein (Csp1) after amphetamine (AMPH) exposure. Bowyer, J.F., Davies, D.L. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  25. Surface staining and cytotoxic activity of heat-shock protein 60 antibody in stressed aortic endothelial cells. Xu, Q., Schett, G., Seitz, C.S., Hu, Y., Gupta, R.S., Wick, G. Circ. Res. (1994) [Pubmed]
  26. Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis. Prakken, B.J., van der Zee, R., Anderton, S.M., van Kooten, P.J., Kuis, W., van Eden, W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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