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Title of Journal: Dig Dis Sci

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Abbravation: Digestive Diseases and Sciences

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Springer US

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DOI

10.1016/j.anl.2005.09.001

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1573-2568

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αLipoic Acid Prevents the Induction of iNOS Gene

Authors: Masanori Yamada Masaki Kaibori Hironori Tanaka Kozo Habara Takeshi Hijikawa Yoshito Tanaka Masaharu Oishi Tadayoshi Okumura Mikio Nishizawa AHon Kwon
Publish Date: 2012/01/03
Volume: 57, Issue: 4, Pages: 943-951
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Abstract

αLipoic acid αLA has been reported to reduce ischemia–reperfusion injury IRI Proinflammatory cytokines stimulate the induction of inducible nitric oxide synthase iNOS gene expression leading to excess production of NO and resulting in liver injury including IRI We hypothesized that inhibition of iNOS induction underlies the protective effects of αLA on the liver The objective was to investigate whether αLA directly influences iNOS induction in cultured hepatocytes which is used as a simple in vitro injury model and the mechanism involvedαLA inhibited the expression of iNOS mRNA and protein dose and timedependently resulting in decreases in NO production αLA had no effects on the degradation of IκB proteins and activation of NFκB In contrast αLA inhibited the upregulation of type I IL1 receptor stimulated by IL1β although αLA had no effect on Akt activation Transfection experiments with iNOS promoterluciferase constructs revealed that αLA had no effect on the transactivation of the iNOS promoter but decreased the stabilization of iNOS mRNA Further αLA inhibited the expression of an iNOS gene antisensetranscript which is involved in iNOS mRNA stabilityResults indicate that αLA inhibits the induction of iNOS gene expression at a posttranscriptional step via iNOS mRNA stabilization rather than promoter activation It may provide useful therapeutic effects through the suppression of iNOS induction involved in liver injury

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