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Seema Somji, John H. Todd, Mary Ann Sens, Scott H. Garrett, and Donald A. Sens

Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, Morgantown, West Virginia, USA

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 µM CdCl₂ 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 Cd²⁺, 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 Cd²⁺ by treating the cells continuously with Cd²⁺ at both lethal and sublethal levels over a 16-day time course. Chronic exposure to Cd²⁺ 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 Cd²⁺, and hsp 70B mRNA was not detected during the 16-day time course. Cd²⁺ 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. Key words: cadmium, gene expression, heat shock, heavy metals, hsc 70, hsp 70, proximal tubule, sodium arsenite. Environ Health Perspect 107:887-893 (1999) . [Online 12 October 1999]

http://ehpnet1.niehs.nih.gov/docs/1999/107p887-893somji/ abstract.html

Address correspondence to D.A. Sens, Department of Pathology, West Virginia University, P.O. Box 9203, Morgantown, WV 26506. Telephone: (304) 293-3212. Fax: (304) 293-6249. E-mail: dsens@wvu.edu

This study was made possible by grant ESO7687 from the National Institute of Environmental Health Sciences, NIH, and by the Department of Pathology Research and Education fund.

Received 1 April 1999 ; accepted 24 June 1999.