Localization of glutamate-cysteine ligase mRNA and protein in mouse kidneyand induction with methylmercury

Methylmercury (MeHg) is a toxicant that targets the kidney among other tiss ues. MeHg accumulates in the kidney, where it indirectly produces oxidative stress due to glutathione depletion and leakage of reactive oxygen species from the mitochondria. Glutathione is believed to have an important role i n protecting the kidney against MeHg toxicity, and MeHg exposure is known t o result in the induction of GSH synthesis through the upregulation of the enzyme glutamate-cysteine ligase (GLCL). GLCL, the rate-limiting enzyme in GSH synthesis, is composed of two subunits, a large catalytic (GLCLc) and a smaller regulatory (GLCLr) subunit. In this study we show that GLCLc and G LCLr mRNAs and GLCLc protein are localized in the paracortical region of th e mouse kidney, the area of the kidney with the hi.-hest MeHg concentration , and that the upregulation of these mRNAs induced by MeHg is also located to the same region. This supports the role of GLCL in protection against Me Hg toxicity in the kidney. (C) 2001 Elsevier Science Ireland Ltd. All right s reserved.