Expression of heat shock protein 60 in human proximal tubule cells exposed to heat, sodium arsenite and CdCl(2).
The expression of hsp 60 mRNA and protein were determined in human proximal tubule cells (HPT) exposed to lethal and sub-lethal concentrations of Cd(2+) under both acute and extended conditions of exposure. It was demonstrated that HPT cells exhibited the classic heat shock response when subjected to a physical (heat) or chemical stress (sodium arsenite). Heat stress, elevated temperature at 42.5 degrees C for 1 h, caused an increase in both hsp 60 mRNA and protein following removal of the stress. Similar results were obtained when the cells were subjected to a classic chemical stress of exposure to 100 microM sodium arsenite for 4 h. Acute exposure of HPT cells to 53.4 microM CdCl(2) for 4 h also resulted in an increase in hsp 60 mRNA and protein following removal of the metal. An extended exposure to Cd(2+) was modeled by treating the cells continuously with Cd(2+) at both lethal and sub-lethal levels over a 16-day time course. It was demonstrated that chronic exposure to Cd(2+) failed to increase either hsp 60 mRNA or protein expression in HPT cells, even at concentrations of Cd(2+) that were lethal to the cells during the time course. In fact, hsp 60 protein levels were decreased compared to controls at lethal levels of Cd(2+) exposure. These findings suggest that hsp 60 expression may have two distinct roles when the human proximal tubule cell is exposed to Cd(2+). A protective role through hsp 60 induction when the proximal tubule cell is acutely exposed to Cd(2+) and a deleterious role when hsp 60 protein is down-regulated during extended exposure to Cd(2+).
Somji
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Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, PO Box 9203, Morgantown, WV 26506, USA.
Todd
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Sens
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Garrett
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D018053:Arsenites / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D018834:Chaperonin 60 / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017670:Sodium Compounds / Q000494:pharmacology
D018053:Arsenites; D018834:Chaperonin 60; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; D019256:Cadmium Chloride