Stable transfection of LLC-PK1 cells with human microsomal glutathione S-transferase gene increases haloalkene glutathione S-conjugate formation and cytotoxicity

Biochemical and Biophysical Research Communications
M A Otieno, M W Anders

Abstract

Nephrotoxic haloalkenes undergo glutathione- and cysteine conjugate beta-lyase-dependent bioactivation, and glutathione S-conjugate formation with haloalkenes as substrates is preferentially catalyzed by the hepatic microsomal glutathione S-transferase (mGST). Porcine kidney-derived LLC-PK1 cells, which are competent to bioactivate glutathione and cysteine S-conjugates of haloalkenes, show low mGST activity. Stable transfection of LLC-PK1 cells with the gene encoding mGST would be expected to increase glutathione S-conjugate formation and, therefore, to increase haloalkene cytotoxicity. Transfection of LLC-PK1 cells with human mGST genes resulted in increased expression of mGST protein in microsomal fractions, in increased glutathione S-conjugate formation with hexachloro-1,3-butadiene and 1-chloro-2,4-dinitrobenzene as the substrates, and in increased cytotoxicity of hexachloro-1,3-butadiene. In addition, transfection with mGST gene also increased the activity of cytosolic glutathione S-transferases.

Citations

Feb 3, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Qiang Shi, Yi-jia Lou
Dec 31, 2002·Journal of the American Society of Nephrology : JASN·Danyelle M TownsendMarie H Hanigan

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