Molecular chaperones response

Both the heat and cold shock response are universal and have been studied extensively. The major heat shock proteins (HSPs) are highly conserved. They are involved in the homeostatic adaptation of cells to harsh environmental conditions. Some act as molecular chaperones for protein folding, while others are involved in the processing of denatured polypeptides whose accumulation would be deleterious. The cold shock results in the transient induction of cold shock proteins (CSPs), which include a family of small acidic proteins carrying the cold shock domain. The CSPs appear to be involved in various cellular functions such as transcription, translation and DNA recombination. 

Feder, M.E., and G.E. Hofmann (1999). Heat-shock proteins, molecular chaperones and the stress response Evolutionary and ecological physiology. Annu. Rev. Physiol. 61 243-282. 

Inhibition of Icmt by adenosine and homocysteine or AGGC has also been proposed to induce apoptosis in pulmonary artery ECs by two distinct mechanisms involving Ras and RhoA [75,76]. The first proposed mechanism was the attenuation of Ras-stimulated Erk and Akt signaling. Evidence for this consisted of the ability of active H-Ras to overcome the effects of adenosine and homocysteine, as well as the ability of dominantnegative H-Ras to induce apoptosis in the absence of adenosine and homocysteine [75]. The second mechanism proposed was that inhibition of Icmt induces apoptosis by causing dysfunction of the ER unfolded protein response (UPR), potentially due to a subcellular relocalization, aggregation, and decrease in protein level of the ER molecular chaperone GRP94. This apoptotic phenotype could be rescued upon expression of active RhoA [76]. Overexpression of Icmt-GFP was also found to protect ECs from apoptosis induced by UV, TNFot, and adenosine and homocysteine [75]. 

Heat shock proteins (HSPs) are a family of proteins expressed in almost all organisms from prokaryotes to humans. HSPs were originally described about four decades ago as proteins that were induced in the Drosophila melanogaster in response to a heat stress and hence derive the name HSR However, research over the years has uncovered these proteins to have a multitude of functions. Primarily, all HSPs act as molecular chaperons and assist in proper folding of naive proteins. Furthermore, HSPs have important roles in cellular processes including cell survival, inflammation, immunity, ion channel repair, and others. HSPs are also induced by a variety of stressors. Reactive oxygen species, cytotoxic injury, necrosis, ultraviolet radiation, metals, and many others are some examples. 

In virtually all organisms, enhanced synthesis of heat shock proteins (HSPs) occurs in response to environmental, chemical, and physiological stresses. Some members of the evolutionarily conserved HSP gene family are constitutively expressed and function as molecular chaperones. It has been demonstrated that HSP induction results primarily from the activation of a heat shock transcription factor (HSF) with subsequent binding to heat shock response DNA elements (HSEs) in the enhancer regions of the HSP genes157. Heat shock responses in fish have been recently reviewed by Basu et al.15 and will be discussed in another chapter of this volume, so we will primarily limit our discussions to heat shock responses in zebrafish. 

FUNCTIONAL GENOMIC APPROACHES TO UNDERSTANDING MOLECULAR CHAPERONES AND STRESS RESPONSES... 

Historically, efforts to characterize the cell s basal protein folding and degradation machinery have been spearheaded by the analysis of proteins specifically induced by the classic heat shock response. Yet it is clear that cellular responses to heat and other stresses that compromise protein folding encompass a range of biochemical activities far broader than molecular chaperones and proteases. The availability of complete genomic sequences from a range of eukaryotes, bacteria, and archae,... 

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