World Aquaculture 63 Cellular Stress Response. The generalized stress response at the cellular level is characterized by a family of proteins referred to as heat shock proteins (Hsps). Heat shock protein are highly conserved cellular proteins that have been observed in all organisms, including fish. Extensive studies on model species have revealed three major families of heat shock proteins, such as Hsp90 (85-90 kDa), Hsp70 (68-73 kDa) and low molecular weight Hsp (16-24 kDa). In the unstressed cell, there is a constitutive production of these proteins that are required in various aspects of cellular homeostasis. Hsp70 is known to assist the folding of nascent polypeptide chains, act as a molecular chaperone and mediate the repair and degradation of altered or denatured proteins. Hsp90 is active in supporting various components of cell signaling, including the cytoskeleton, enzymes and steroid hormone receptors. Low molecular weight Hsps have no known constitutive function and seem to be only induced during stress. There is increasing interest in the physiological and protective role of Hsps following the exposure of fish to various environmental stressors. For example, increased levels of various Hsps have been measured in tissues of fish exposed to bacterial pathogens and environmental contaminants, such as heavy metals in industrial effluents, pesticides and polycyclic aromatic hydrocarbons. Mechanism to Control Stress by Heat Shock Proteins. Production of high levels of heat shock proteins can also be triggered by exposure to various kinds of environmental stress conditions, such as infection, inflammation, exercise, exposure of the cell to toxins, starvation, hypoxia, nitrogen deficiency or water deprivation. Consequently, heat shock proteins are also referred to as stress proteins and their up-regulation is sometimes described more generally as part of the stress response. An increase in damaged or abnormal proteins may bring Hsps into action. Role as Chaperone. Heat shock proteins function as intracellular chaperones for other proteins. They play an important role in protein-protein interactions, such as folding and assisting in the establishment of proper protein conformation (shape) and prevention of unwanted protein aggregation. By helping to stabilize partially unfolded proteins, Hsps aid in transporting proteins across membranes Table 1. Most important members of prokaryotic and eukaryotic heath stock proteins and their functions. Approximate molecular Prokaryotic Eukaryotic weight (kDa) proteins proteins Function 10 GroES Hsp10 20-30 GrpE HspB group of Hsp. Eleven members in mammals including Hsp27 or HspB1 40 DnaJ Hsp40 Co-factor of Hsp70 60 GroEL, 60kDa antigen Hsp60 Involved in protein folding, after its post-translational import to the mitochondrion/chloroplast. 70 DnaK HspA group, including Protein folding and unfolding, provides Hsp71, Hsp70, Hsp72, thermotolerance to cell on exposure to Grp78 (BiP), Hsx70 heat stress. Also prevents protein folding during post-translational import into the mitochondria/chloroplast. 90 HtpG, C62.5 HspC group, including Maintenance of steroid receptors and Hsp90, Grp94 transcription factors. 100 ClpB, ClpA, ClpX Hsp104, Hsp110 Tolerance to extreme temperature. within the cell. Some members of the Hsp family are expressed at low to moderate levels in all organisms because of their essential role in protein maintenance. Housekeeping. Heat-shock proteins also occur under non-stress conditions, simply monitoring a cell’s proteins. As an example, Hsps carry old proteins to a cell’s “recycling bin” and help newly synthesized proteins fold properly. These activities are part of a cellular repair system, called the cellular stress response or heat-shock response. Cardiovascular. Heat shock proteins (Hsp90, Hsp84, Hsp70, Hsp27, Hsp20 and alpha-B-crystallin) appear to serve a major cardiovascular role. Hsp 90 binds both endothelial nitric oxide synthase and soluble guanylate cyclase, which in turn are involved in vascular relaxation. Hsp 20 phosphorylation correlates well with smooth muscle relaxation and is one major phosphoprotein involved in the process. Hsp 20 is involved in the smooth muscle phenotype during development and plays a major role in preventing platelet aggregation, cardiac myocyte function, and prevention of apoptosis, skeletal muscle function and muscle insulin response. Hsp 27 is a major phosphoprotein during muscle con-
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