Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the nadph oxidase, Nox4, in mesangial cells

Anu Shah, Ling Xia, Howard Goldberg, Ken W. Lee, Susan E. Quaggin, I. George Fantus*

*Corresponding author for this work

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Background: Thioredoxin-interacting protein (TxNIP) is up-regulated by high glucose (HG), inhibits the antioxidant, thioredoxin, and thereby is implicated in oxidative stress. Results: TxNIP deficiency protects mesangial cells from HG-induced oxidative stress and increased collagen by blocking mitochondrial glucose metabolism, NADPH oxidase, and Nox4. Conclusion: TxNIP controls ROS generation by regulating the TCA cycle versus glycolytic glucose flux. Significance: Inhibition of TxNIP is a promising approach to treat glucose toxicity.

Original languageEnglish (US)
Pages (from-to)6835-6848
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number10
DOIs
StatePublished - Mar 8 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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