Heat shock gene expression and development of translational thermotolerance in human hepatoblastoma cells.
Synthesis of heat shock proteins is a conserved cellular response to disparate environmental stresses, including circulatory shock/resuscitation. Heat shock proteins are believed to play a cytoprotective role within the cell. To understand the regulation of the heat shock response, the kinetics of expression of the major inducible heat shock protein (hsp-72) was studied in a simple model: human hepatoblastoma (HepG2) cells in culture under thermal stress. At both mild (41 degrees C) and moderate (43 degrees C) heat shock temperatures, new synthesis of hsp-72 was proportional to the steady-state level of hsp-72 mRNA, suggesting that the regulation of the heat shock response in these cells is primarily transcriptional. Moderate but not mild thermal stress attenuated total protein synthesis, a consequence of inhibition of both the uptake of amino acids by the cells and the incorporation of amino acids into polypeptides. The thermal inhibition of protein synthesis was far more severe in naive cells than in cells previously heat-stressed. The development of translational tolerance of heat-primed cells correlates with the content of hsp-72 accumulated following the initial stress. These data suggest that expression of hsp-72 may be important in maintaining hepatic protein synthesis after stress.
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-5612.
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A
De Maio
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SC
Beck
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Buchman
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D008715:Methionine