Localization of glutamate-cysteine ligase mRNA and protein in mouse kidney and induction with methylmercury.
Methylmercury (MeHg) is a toxicant that targets the kidney among other tissues. 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 in protecting the kidney against MeHg toxicity, and MeHg exposure is known to 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 GLCLr mRNAs and GLCLc protein are localized in the paracortical region of the mouse kidney, the area of the kidney with the highest 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 MeHg toxicity in the kidney.
Díaz
D
D
Department of Environmental Health, University of Washington, Mail Box 354695, Seattle, WA 98195, USA.
Krejsa
C M
CM
Kavanagh
T J
TJ
D000818:Animals; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D008767:Methylmercury Compounds; D012333:RNA, Messenger; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione