Toxicology Letters 115 (2000) 127 – 136
Expression of heat shock protein 60 in human proximal
tubule cells exposed to heat, sodium arsenite and CdCl
2
Seema Somji, John H. Todd, Mary Ann Sens, Scott H. Garrett,
Donald A. Sens *
Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia Uniersity, PO Box 9203, Morgantown,
WV 26506, USA
Received 8 October 1999; received in revised form 19 January 2000; accepted 20 January 2000
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°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 M sodium arsenite for 4 h. Acute exposure of HPT cells to 53.4 M 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 +
. © 2000 Elsevier Science Ireland Ltd.
All rights reserved.
Keywords: Cadmium; Heavy metals; Heat shock; hsp 60; Gene expression; Sodium arsenite; Proximal tubule; Chaperones; Heat
shock proteins; Stress response
www.elsevier.com/locate/toxlet
1. Introduction
A major weapon in the cell’s armamentarium
for protection against and recovery from both
physical and chemical environmental insult is the
heat shock response, named due to its initial
* Corresponding author. Tel.: +1-304-2933212; fax: +1-
304-2936249.
E-mail address: dsens@hsc.wvu.edu (D.A. Sens)
0378-4274/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII:S0378-4274(00)00183-1