title: Expression of heat shock protein 60 in human proximal tubule cells exposed to heat, sodium arsenite and CdCl(2).
abstract: 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+).
authors.affiliation: Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, PO Box 9203, Morgantown, WV 26506, USA.
authors.forename: S
authors.initials: S
authors.lastname: Somji
authors.forename: J H
authors.initials: JH
authors.lastname: Todd
authors.forename: M A
authors.initials: MA
authors.lastname: Sens
authors.forename: S H
authors.initials: SH
authors.lastname: Garrett
authors.forename: D A
authors.initials: DA
authors.lastname: Sens
mesh_terms: 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
chemical_list: D018053:Arsenites; D018834:Chaperonin 60; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; D019256:Cadmium Chloride