Regulation of survival gene hsp70

Abstract

Rapid expression of the survival gene, inducible heat shock protein 70 (hsp70), is critical for mounting cytoprotection against severe cellular stress, like elevated temperature. Hsp70 protein chaperones the refolding of heatdenatured peptides to minimize proteolytic degradation as a part of an eukaryotically conserved phenomenon referred to as the heat shock response. The physiologic stress associated with exercise, which can include elevated temperature, mechanical damage, hypoxia, lowered pH, and reactive oxygen species generation, may promote protein unfolding, leading to hsp70 gene expression in skeletal myofibers. Although the pre-transcriptional activation of hsp70 gene expression has been thoroughly reviewed, discussion of downstream hsp70 gene regulation is less extensive. The purpose of this brief review was to examine all levels of hsp70 gene regulation in response to heat stress and exercise with a special focus on skeletal myofibers where data are available. In general, while heat stress represses bulk gene expression, hsp70 mRNA expression is enhanced. Posttranscriptionally, intronless hsp70 mRNA circumvents a host of decay pathways, as well as heat stress-repressed premRNA splicing and nuclear export. Pre-translationally, hsp70 mRNA is excluded from stress granules and preferentially translated during heat stress-repressed global cap-dependent translation. Post-translationally, nascent Hsp70 protein is thermodynamically stable at elevated temperatures, allowing for the commencement of chaperoning activity early after synthesis to attenuate the heat shock response and protect against subsequent injury. This review demonstrates that hsp70 mRNA expression is closely coupled with functional protein translation.

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice

“…Consistent with this finding, overexpression of HSP genes increased longevity in Drosophila, Caenorhabditis elegans, and vertebrates (1,8,9). Hsp70 is the major cytoprotective molecular chaperone with many different functions in the cell (10)(11)(12). Observations suggest that genetic variants of the Hsp70 family contribute to longevity in a wide range of organisms (9,13,14).…”

Characterization of the small heat shock protein Hsp27 gene in Chironomus riparius (Diptera) and its expression profile in response to temperature changes and xenobiotic exposures

“…They have important functions in many physiological processes, and are particularly relevant when cells are under stressful conditions as chaperones for the maintenance of correct protein folding (Nolen and Morimoto 2002;Silver and Noble 2012). HSPs were first discovered under heat shock and were later found to be highly abundant in cells submitted to many other chemical and physical stimuli in a wide range of species.…”

Effect of Forced Exercise (Tap Stress) on Drosophila Melanogaster and Efficacy of Abhrak Bhasma as Dietary Supplement.

“…Besides the catalase gene, other stress-related genes such as cncC and hsp70, through their products, play an important role in the management of various stresses [9,34]. In this regard, diet supplement of AB seems to have a better protective role in countering the effect of tap stress.…”

“…The non-catalytic components consist of various nonspecific reducing moieties in the cell, including certain vitamins and glutathione (GSH) system [7,8]. In addition, activation factors synthesized through the translation of Cap "n" collar C (cncC) and heat shock protein (hsp) genes help in managing the oxidative stress [9].…”