title: Expression of the constitutive and inducible forms of heat shock protein 70 in human proximal tubule cells exposed to heat, sodium arsenite, and CdCl(2).
abstract: We determined the expression of the constitutive (hsc 70) and inducible (hsp 70) forms of heat shock protein 70 mRNA and protein in human proximal tubule (HPT) cells exposed to lethal and sublethal concentrations of Cd(+2) under both acute and extended conditions of exposure. The HPT cells exhibited the classic heat shock response when subjected to a physical (heat) or chemical stress (sodium arsenite); hsc 70 mRNA and protein levels were constant or slightly increased, whereas hsp 70 mRNA and protein were greatly elevated. Acute exposure to 53.4 microM CdCl(2) for 4 hr failed to increase either hsc 70 mRNA or protein, a finding similar to that observed under classic conditions of stress. However, under identical conditions of acute exposure to Cd(2+), the expected increase in hsp 70 protein level was suppressed as compared to that found under classic conditions of physical or chemical stress. The decrease in hsp 70 protein level correlated to the reduced expression of mRNA from the hsp 70B gene. The expression of mRNA from the hsp 70A and hsp 70C genes was similar to that found when the cells were treated with heat shock or sodium arsenite. We modeled an extended exposure to Cd(2+) by treating the cells continuously with Cd(2+) at both lethal and sublethal levels over a 16-day time course. Chronic exposure to Cd(2+) failed to increase either hsc 70 mRNA or protein levels in the HPT cells at a nonlethal dosage level and decreased hsc 70 mRNA and protein levels late in the time course of lethal exposure. Under identical conditions, the expression of hsp 70 protein remained at basal levels that were only marginally detectable throughout the time course. Hsp 70A and hsp 70C mRNA levels were unaltered by extended exposure to Cd(2+), and hsp 70B mRNA was not detected during the 16-day time course. Cd(2+) is a poor inducer of hsc 70 and hsp 70 in the proximal tubule under both acute and long-term exposure. These results reinforce the fact that the expression of hsp 70 protein does not result from the transcription of a single gene, but is derived from what may be a complex interplay of several underlying genes.
authors.affiliation: Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, Morgantown, West Virginia, 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 / Q000009:adverse effects* / Q000494:pharmacology; D019256:Cadmium Chloride / Q000009:adverse effects* / Q000494:pharmacology; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D017670:Sodium Compounds / Q000009:adverse effects* / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D018053:Arsenites; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; D019256:Cadmium Chloride