Heat-shock protein system

A unique property of nuclear steroid hormone leceptois is that they associate with a large multicomponent protein complex of chaperones, the Hsp90 (heat-shock protein) system. (Chaperones which associate with nascent polypeptide chains and assist them to fold are named chaperonins, whereas chaperones are proteins which associate with polypeptide chains, post-translationally) (Fig. 11.6). 

Matthews, R.C., Bumie, J.P., Howat, D., Rowland, T., Walton. F. (1991). Autoantibody to heat shock protein 90 can mediate protection against systemic candidosis. Immunology 74,20-24. 

To test the irritancy potential of substances, two tests which can reliably distinguish between skin corrosives and noncorrosives are endorsed by the European Centre for the Validation of Alternative Methods (ECVAM). The testing procedures are based on the transcutaneous electrical resistance (TER) measurements of rat skin and on a human skin model. Both test systems [141-145] will be briefly outlined below. Nevertheless, these tests are not suited for the group of mild irritants which do not induce an acute effect on the barrier function. For those substances, new markers need to be evaluated. First results are available for heat shock protein 27 where higher levels were observed in skin models after exposure to mildly irritating chemicals [146, 147]. 

Details of the activation and transport into the nucleus remain unknown. It is assumed that the complex between receptor and hormone and the loosely associated heat shock proteins reaches the nucleus via a protein transport system. After dissociation of the heat shock proteins, the hormone-receptor complex is capable of specific binding on the HRE and of transactivation. 

The role of the IF, and particularly the keratin filament system, in resisting the forces of mechanical stress has been well established. However, IFs also play a role in countering metabolic stress. Perhaps the best example is the cytoprotective role played by the simple epithelial keratins, K8/18. However, vimentin, desmin, peripherin, GFAP, the lens proteins phakinin, and filensin and other keratins have also been shown to associate with members of the small heat shock protein (HSP) family, including HSP27 and aB-crystallin (reviewed in Coulombe and Wong, 2004 Marceau et al., 2001 Nicholl and Quinlan, 1994). 

Hashimoto K., Watanabe K., Nishimura T., Iyo M., Shirayama Y., and Minabe Y. (1998). Behavioral changes and expression of heat shock protein hsp-70 mRNA, brain-derived neurotrophic factor mRNA, and cyclooxygenase-2 mRNA in rat brain following seizures induced by systemic administration of kainic acid. Brain Res. 804 212-223. 

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