Heat shock protein 90

During the period of aging, posttranslational modified proteins and advanced glycosylation end products, which accumulate in tissues, might chronically stimulate HSP production, and affect the basal synthesis of this cell defense mechanism. In this regard, acutely induced HSP synthesis does decrease with aging. However, since the effect of age on the basal expression of HSP70 had not previously been addressed, Maiello and associates (M3) studied the age-dependent basal 

As previously noted, caloric restriction (CR) is the only known effective experimental manipulation shown to retard the aging process. CR has also been shown to alter various age-related processes. Moore and co-workers (M14) studied the effects of aging and CR on the ability of alveolar macrophages to produce HSP70. Here, they isolated alveolar macrophages from young (4-6 months) and old 

Cataracts and macular degeneration Diabetes mellitus Immune system disorders Neurodegenerative disorders Neuroendocrine disorders Nutritional deficiencies 

Although aging and disease are distinctly separate processes, aging predisposes one to numerous diseases/disorders (Table 4). Several of the major age-related diseases will be briefly discussed in the following sections. 

Atherosclerosis ( hardening of the arteries ) is clearly the most common disease process leading to disability and death in the industrialized countries. That is, coronary artery disease (CAD) was the number 1 cause of death in the United States, while cerebrovascular disease (stroke and ischemic dementia) was the third major 

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Trehalose is particularly well-suited for this purpose and has been shown to be superior to other polyhydroxy compounds, especially at low concentrations. Support for this novel idea comes from studies by P. A. Attfield, which show that trehalose levels in the yeast Saccharomyces cerevisiae increase significandy during exposure to high salt and high growth temperatures—the same conditions that elicit the production of heat-shock proteins ... 

Molecular chaperone (relative molecular mass 78 K) found in the lumen of the ER. BiP is related to the Hsp70 family of heat-shock proteins and was originally described as immunoglobulin heavy chain binding protein. 

Molecular chaperones, stress proteins (note not all stress proteins are molecular chaperones and not all molecular chaperones are stress proteins) Heat shock proteins (Hsp) Polypeptide chain binding proteins... 

Hsp70 is a molecular chaperone (relative molecular mass 70 kD) found in different compartments of eucaryotic cells. Hsp70 was originally described as heat shock protein 70. 

Similar to nNOS, Ca2+-activated calmodulin is important for the regulation of eNOS activity. However, several other proteins interact with eNOS and regulate its activity. Heat shock protein 90 (hsp90) is found associated with eNOS and probably acts as an allosteric modulator that activates the enzyme. Caveolin-1 binds eNOS and directs it to caveolae. Caveolin-1 is viewed as an inhibitor of eNOS activity, which is being replaced by CaM upon activation of endothelial cells [2]. 

Cardiac hypertrophy appears to be mediated by HS proteins (Izumo et al., 1988). Cardiac myocytes exposed to a hemodynamic stress have been found to increase their levels of heat shock proteins (Delcayre et al., 1988). Although experiments involving interference with HS protein synthesis were not done in these studies. 

Ab, B.K., Kiessling, R., Van, E.J.D., Thole, J.E.. Kumararatne, D.S., Pisa, P., Wondimu. A., Ottenhoff, T.H. (1990). Induction of antigen-specific CD4+ HLA-DR restricted cytotoxic lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65 kDa heat shock protein. Eur. J. Immunol. 20, 369-377. 

Aguas, A., Esaguy, N., Sunkel, C.E., Silva, M.T. (1990). Cross-reactivity and sequence homology between the 65 kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. Infect. Immun. 58, 1461-1470. 

Anderson, R.L., Tao, T.W., Betten, D.A., Hahn, G.M. (1986). Heat shock protein levels are not elevated in heat resistant B16 melanoma cells. Radiat Res. 105,240-246. 

Atkinson, B.G., Blaker, T,W Tomlinson, J., Dean, R.L. (1990). Ferritin is a translationally regulated heat shock protein of avian reticulocytes. J. Biol. Chem. 265, 14156-14162. 

Aujame, L. Firko, H. (1988). The major inducible heat shock protein hsp68 is not required for acquisition of thermal resistance in mouse plasmacytoma cell lines. Mol. Cell. Biol. 8,5486-5494. 

Bagchi, M.K., Tsai, S.Y., Tsai, M.J., O Malley, B.W. (1991). Progesterone enhances target gene transcription by receptor free of heat shock proteins hsp90, hsp56, and hsp70. Mol. Cell. Biol. 11. 4998-5004. 

Bansal, G.S., Norton, P.M., Latchman, D.S. (1991). The 90-kDa heat shock protein protects matiunalian cells from thermal stress but not from viral infection. Exp. Cell Res. 195,303-306. 

Beere, H.M., Morimoto, R.I., Hickman, J.A. (1993). Investigations of mechanisms of drug-induced changes in gene expression N methylformamide-induced changes in synthesis of the M(r) 72,000 constitutive heat shock protein during commitment of HL-60 cells to granulocyte differentiation. Cancer Res. 53, 3034—3039. 

Blake, M.J., Udelsman, R., Feulner, G.J., Norton, D.D., Holbrook, N.J. (1991). Stress induced heat shock protein 70 expression in adrenal cortex An ACTH-sensitive. age-dependent response. Proc. Natl. Acad. Sci. USA 88, 9873-9877,... 

Bresnick, E.H., Sanchez, E.R., Pran, W.B. (1988). Relationship between glucocorticoid receptor steroid binding capacity and association of the Mr 90.000 heat shock protein with the unliganded receptor. J. Steroid Biochem. 30,267-269. 

Cadepond, F., Schweizeer, G.G., Segatd, M.I., Jibard, N., Hollenberg, S.M., Giguere, V., Evans, R.M., Baulieu, E. (1991). Heat shock protein 90 as a critical factor in maintaining glucocorticosteroid receptor in a nonfunctional state. J. Biol. Chem. 266, 5834-5841. 

Chang, C.C., Konno, S., Wu, J.M. (1991). Enhanced expression of heat shock protein and mRNA synthesis by type I interferon in human HL-60 leukemic cells. Biochem Inti. 24, 369-377. 

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