Sodium arsenite and heat shock induce stress proteins in precision-cut rat liver slices.
The present study was undertaken to investigate the usefulness of stress proteins as early, sensitive indicators of hepatotoxicity. Induction of stress protein synthesis in precision-cut rat liver slices was examined following in vitro exposure to sodium arsenite or heat shock. Precision-cut rat liver slices were incubated with 10(-5) or 10(-6) M sodium arsenite for 2, 4 or 8 h in the presence of 35S-methionine or exposed to hyperthermia (42.5 +/- 0.5 degrees C) for 45 min and then incubated with 35S-methionine for 2, 4 or 8 h. Fluorographic analysis indicated an increase in the synthesis of HSP 70 and HSP 90 family of proteins by both treatments. Immunoblot analysis demonstrated that there was a specific induction of HSP 72 and HSP 90. Induction of HSP 70 was greater than that of HSP 90 by both treatments. Stress protein induction occurred at earlier times by concentrations of arsenite which did not alter other viability parameters such as leakage of intracellular K+ or total protein synthesis. The results indicated that induction of stress proteins has the potential usefulness as an early biomarker of arsenite toxicity.
Wijeweera
J B
JB
Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85724, USA.
Thomas
C M
CM
Gandolfi
A J
AJ
Brendel
K
K
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D004591:Electrophoresis, Polyacrylamide Gel; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects*; D015151:Immunoblotting; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000737:chemistry / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000633:toxicity*; D013439:Sulfhydryl Reagents / Q000633:toxicity*
D018053:Arsenites; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; C017947:sodium arsenite; D008715:Methionine; D007930:Leucine; D011188:Potassium