Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular and biochemical events which transduce chemical insults into signals for increased expression of the stress-responsive gene gadd 153 were investigated using nephrotoxic cysteine conjugates. In LLC-PK1 cells, cysteine conjugate toxicity is initiated by covalent binding, but depletion of cellular thiols, an increase in cytosolic free calcium, and lipid peroxidation couple the binding to cell death (Chen, Q., Jones, T. W., Brown, P. C., and Stevens, J. L. (1990) J. Biol. Chem. 265, 21603-21611; Chen, Q., Jones, T. W., and Stevens, J. L. (1991) Toxicologist 11, 101, 1991). Three different toxic cysteine conjugates induced gadd 153 mRNA. With S-(1,2-dichlorovinyl)-L-cysteine (DCVC), the induction was both concentration and time-dependent. Preventing the metabolism of DCVC and covalent binding of DCVC-derived reactive metabolites to cellular macromolecules with the beta-lyase inhibitor (aminooxy)acetic acid blocked the induction. However, buffering free calcium with a cell permeable calcium chelator or blocking lipid peroxidation with an antioxidant did not affect the induction of gadd 153 mRNA by DCVC even though these treatments inhibit toxicity. These data suggest that covalent binding of reactive metabolites to cellular macromolecules may serve as a primary signal for the induction of gadd 153 mRNA by nephrotoxic cysteine conjugates. Interestingly, the sulfhydryl agent dithiothreitol, which was nontoxic and prevented the toxicity of DCVC, also induced an increase in gadd 153 mRNA. When both dithiothreitol and DCVC were added to cells, there were no inhibitory or additive effects on expression. Therefore, cellular thiol-disulfide status may also play a role in gadd 153 induction.
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PMID:Activation of the growth arrest and DNA damage-inducible gene gadd 153 by nephrotoxic cysteine conjugates and dithiothreitol. 156 75

Variations in liver and kidney kynurenine aminotransferase (KAT) activity in Pittsburg-Yoshida, Brown-Norway, albino Wistar, Sprague-Dawley, Long Evans and heterozygous Gunn rats were studied. In liver, values of KAT specific activity, expressed as mumoles of kynurenic acid formed per hour per mg of protein, were different in the groups of Brown-Norway and Pittsburg-Yoshida rats versus Long Evans and Sprague-Dawley rats. The activity expressed as mumoles of kynurenic acid per g of fresh liver showed other differences, being significantly higher in Gunn with respect to other strains of rats and lower in Pittsburg-Yoshida and Brown-Norway rats. In addition, KAT activity was significantly lower in Pittsburg-Yoshida than in Brown-Norway rats. In kidney, the specific activity of kynurenine aminotransferase showed significant differences in the values of Sprague-Dawley and Long Evans rats versus the other strains. The activity expressed per g of fresh tissue was significantly higher in Wistar, Sprague-Dawley, Long Evans and Gunn than in Pittsburg-Yoshida and Brown-Norway rats. No significant differences were found in values between hyperlipidemic Pittsburg-Yoshida and their control Brown-Norway rats. These results high-light the importance of considering various rat strains when inbred animal experimental models are used.
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PMID:Liver and kidney kynurenine aminotransferase activity in different strains of rats. 1072 Nov 11