INCREASED LEVELS OF GLUTATHIONE-S TRANSFERASES AND APPEARANCE OF NOVEL ALPHA-CLASS ISOENZYMES IN KIDNEYS OF MICE EXPOSED TO MERCURIC-CHLORIDE .1. BIOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDIES

Glutathione S transferases (GST) are a family of enzymes that detoxify electrophilic xenobiotics. This enzyme family was examined in kidneys of mice exposed to mercuric chloride, a known nephrotoxin, because GS T have been shown to protect cells against toxicant-induced damage and may serve as biomarkers for toxicant exposure. The purpose of this st udy was to determine the effect of mercuric chloride on GST activity, isoenzyme levels, and cellular localization in the kidney of Swiss Web ster mice. The cellular localizations of alpha, mu, and pi class GST i n the kidneys of control and mercuric chloride treated mice were studi ed immunohistochemically. The GST isoenzyme levels were measured by hi gh-performance liquid chromatography. The mice treated with mercuric c hloride had (1) increased amounts of GSTA1/A2 protein in kidney homoge nates as compared with controls when analyzed by chromatography and el ectrophoresis; (2) two new isoforms of the alpha isoenzyme in kidney a s demonstrated by Western blot, polyacrylamide gel electrophoresis, an d high-performance liquid chromatography, and (3) increased reactivity between antibodies, against GSTA1/A2 or GSTM1 isoenzymes, and cells i n the proximal and distal renal tubules as shown by immunohistochemica l techniques. The authors conclude that the GSTA1/A2 may protect those cells in the proximal and distal tubules of the renal cortex from tox icant effects of mercuric chloride. This would be one general mechanis m for cell protection against a wide variety of toxicants including he avy metals and halogenated aromatics.