Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age‐related muscle dysfunction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154339/1/fsb2fj030395fje-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154339/2/fsb2fj030395fje.pd

Effect of lifelong overexpression of HSP70 in skeletal muscle on age‐related oxidative stress and adaptation after nondamaging contractile activity

[EN] Skeletal muscle aging is characterized by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe injury. The ability of muscles of old mice to produce heat shock proteins (HSPs) in response to stress is severely diminished. Studies in our laboratory using HSP70 overexpressor mice demonstrated that lifelong overexpression of HSP70 in skeletal muscle provided protection against damage and facilitated successful recovery after damage in muscles of old mice. The mechanisms by which HSP70 provides this protection are unclear. Aging is associated with the accumulation of oxidation products, and it has been proposed that this may play a major role in age-related muscle dysfunction. Muscles of old wild-type (WT) mice demonstrated increased lipid peroxidation, decreased glutathione content, increased catalase and superoxide dismutase (SOD) activities, and an inability to activate nuclear factor (NF)- B after contractions in comparison with adult WT mice. In contrast, levels of lipid peroxidation, glutathione content, and the activities of catalase and SOD in muscles of old HSP70 overexpressor mice were similar to adult mice and these muscles also maintained the ability to activate NF- B after contractions. These data provide an explanation for the preservation of muscle function in old HSP70 overexpressor mice.—Broome, C. S., Kayani, A. C., Palomero, J., Dillmann, W. H., Mestril, R., Jackson, M. J., McArdle, A. Effect of lifelong overexpression of HSP70 in skeletal muscle on age-related oxidative stress and adaptation after nondamaging contractile activity

Heat Shock And Developmental Activation Of The D Melanogaster Hsp23 Gene Are Mediated By Different Mechanisms: Identification Of A Signal Involved In Developmental Gene Regulation

The regulation of the Drosophila melanogaster hsp23 gene by heat shock in injected Xenopus oocytes and by heat shock and ecdysterone in transfected hormone-sensitive Drosophila melanogaster cells has been analyzed by measuring activites of hsp-E. coli beta-galactosidase hybrid genes. Mutational analysis identified multiple, distinct promoter elements. A sequence element which also occurs in the promoters of a number of other genes that are specifically expressed in late larvae or early pupae was shown to be essential for the ecdysterone- but not for the heat-regulated activity of the hsp23 gene; this element may represent a binding site(s) for an ecdysterone-receptor complex. Mutant promoters that can only be activated either by heat shock or by hormone have been constructed. Thus, the two types of regulation of the hsp23 gene can function completely independent of each other

Overexpression of heat shock proteins differentially modulates protein kinase C expression in rat neonatal cardiomyocytes

Previous studies have suggested that protein kinase C (PKC) is involved in heat shock protein (Hsp)–mediated cardioprotection. Therefore, we wanted to determine whether overexpression of Hsps modulates PKC expression, which will give us further insight into understanding the mechanism by which Hsps and PKC interact to protect cells from stress-induced injury. Specifically, we overexpressed the inducible form of Hsp70 (Hsp70i) or Hsp90 in rat neonatal cardiomyocytes and evaluated PKCδ or PKCɛ expression by immunoblotting and immunofluorescent confocal microscopy. Western analysis showed that overexpression of Hsp70i or Hsp90 decreased PKCɛ expression. However, overexpression of Hsp70i or Hsp90 did not modify PKCδ expression over control levels. Overexpression of constitutively active PKCδ or PKCɛ increased Hsp70i expression over control levels. The data suggest that overexpression of Hsps differentially modulates expression of PKC isoforms in rat neonatal cardiomyocytes. Furthermore, PKC may directly play a role in Hsp-mediated cardioprotection by upregulating Hsp70i expression