期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 19, 期 12, 页码 1321-1336出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2012.5010
关键词
-
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-056649]
- Charles University [PRVOUK P24/LF1/3, UNCE204011/2012]
Aims: To define the consequences of loss of cysteine dioxygenase (CDO) on cysteine metabolism at the tissue level, we determined levels of relevant metabolites and enzymes and evidence of H2S/HS- (gaseous hydrogen sulfide and its conjugate base) toxicity in liver, pancreas, kidney, and lung of CDO-/- mice that were fed either a taurine-free or taurine-supplemented diet. Results: CDO-/- mice had low tissue and serum taurine and hypotaurine levels and high tissue levels of cysteine, consistent with the loss of CDO. CDO-/- mice had elevated urinary excretion of thiosulfate, high tissue and serum cystathionine and lanthionine levels, and evidence of inhibition and destabilization of cytochrome c oxidase, which is consistent with excess production of H2S/HS-. Accumulation of cystathionine and lanthionine appeared to result from cystathionine -synthase (CBS)-mediated cysteine desulfhydration. Very high levels of hypotaurine in pancreas of wild-type mice and very high levels of cystathionine and lanthionine in pancreas of CDO-/- mice were observed, suggesting a unique cysteine metabolism in the pancreas. Innovation: The CDO-/- mouse model provides new insights into tissue-specific cysteine metabolism, particularly the role of pancreas in metabolism of excess cysteine by CBS-catalyzed reactions, and will be a useful model for studying the effects of excess endogenous production of H2S/HS-. Conclusion: The CDO-/- mouse clearly demonstrates that H2S/HS- production in tissues can exceed the capacity of the animal to oxidize sulfide to sulfate and demonstrates that pancreas and lung are more susceptible to toxicity from endogenous H2S/HS(-)production than are liver and kidney. Antioxid. Redox Signal. 19, 1321-1336.
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