Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells

Balachandar Venkatesan, Lenin Mahimainathan, Falguni Das, Nandini Ghosh-Choudhury, Goutam Ghosh Choudhury

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen peroxide (H2O 2) reduced the expression of catalase. H2O2 increased phosphorylation of Akt kinase in a dose-dependent and sustained manner with a concomitant increase in the phosphorylation of FoxO1 transcription factor. Further analysis revealed that H2O2 promoted rapid activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase activity, resulting in the attenuation of FoxO1 phosphorylation and preventing the down regulating effect of H2O2 on catalase protein level. Dominant negative Akt attenuated the inhibitory effect of H 2O2 on expression of catalase. Constitutively active FoxO1 increased the expression of catalase. However, dominant negative FoxO1 inhibited catalase protein level. Catalase transcription was reduced by H 2O2 treatment. Furthermore, expression of dominant negative Akt and constitutively active FoxO1 increased catalase transcription, respectively. These results demonstrate that ROS downregulatethe expression of catalase in mesangial cells by PI 3 kinase/Akt signaling via FoxO1 as a target.

Original languageEnglish (US)
Pages (from-to)457-467
Number of pages11
JournalJournal of Cellular Physiology
Volume211
Issue number2
DOIs
StatePublished - May 1 2007

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ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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