Stressor-specific induction of heat shock proteins in rat hepatoma cells.
In order to determine whether induction of specific stress proteins is dependent on a given stressor and whether induction of these proteins is linked to survival, Reuber H35 rat hepatoma cells were exposed to five different environmental stressors (heat shock, arsenite, cadmium, dinitrophenol and ethanol). The effect of these stressors was studied on cell survival as well as on inhibition and recovery of protein synthesis and on induction of heat shock proteins (hsps). In this article, we present evidence that several well-known hsp-inducers fail to stimulate specific hsps in a degree that is comparable to the induction of these hsps by heat shock. Most evidently, hsp60 is not induced by cadmium-treatment, whereas hsp100 is hardly induced by sodium arsenite. Treatment with DNP only slightly induces hsp68 and hsp84, whereas no detectable induction of hsps is observed after treatment with ethanol. In contrast, treatment with cadmium raises the amount of hsp28 to a higher level as compared to heat shock. A comparison of the stressor-specific induction of major hsps was also made under conditions of similar impact on cellular physiology: (a) stressor conditions up to the critical point that cell death starts to occur, and (b) conditions of iso-survival (50%). We conclude that hsps cannot be simply used as a general risk-assessment tool, and that the validation of stressor-specific risk-assessment warrants further research with larger groups of proteins.
Wiegant
F A
FA
Department of Molecular Cell Biology, University of Utrecht, The Netherlands.
Souren
J E
JE
van Rijn
J
J
van Wijk
R
R
D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D008114:Liver Neoplasms, Experimental; D008670:Metals / Q000633:toxicity; D051381:Rats; D014407:Tumor Cells, Cultured
D018053:Arsenites; D004140:Dinitrophenols; D006360:Heat-Shock Proteins; D008670:Metals; D002104:Cadmium; D000431:Ethanol; C015001:arsenite