PMID: 15357004Sep 11, 2004Paper

PKC downstream of Pl3-kinase regulates peroxynitrite formation for Nrf2-mediated GSTA2 induction

Archives of Pharmacal Research
Sang Geon Kim, Sun Ok Kim

Abstract

The protective adaptive response to electrophiles and reactive oxygen species is mediated by the induction of phase II detoxifying genes including glutathione S-transferases (GSTs). NF-E2-related factor-2 (Nrf2) phosphorylation by protein kinase C (PKC) is a critical event for its nuclear translocation in response to oxidative stress. Previously, we have shown that peroxynitrite plays a role in activation of Nrf2 and Nrf2 binding to the antioxidant response element (ARE) via the pathway of phosphatidylinositol 3-kinase (Pl3-kinase) and that nitric oxide synthase in hepatocytes is required for GSTA2 induction. In view of the importance of PKC and Pl3-kinase in Nrf2-mediated GST induction, we investigated the role of these kinases in peroxynitrite formation for GSTA2 induction by oxidative stress and determined the relationship between PKC and Pl3-kinase. Although PKC activation by phorbol 12-myristate-13-acetate (PMA) did not increase the extents of constitutive and inducible GSTA2 expression, either PKC depletion by PMA or PKC inhibition by staurosporine significantly inhibited GSTA2 induction by tert-butylhydroquinone (t-BHQ) a prooxidant chemical. Therefore, the basal PKC activity is requisite for GSTA2 induction. 3-Morpholin...Continue Reading

References

Oct 12, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H E MarshallJ S Stamler
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·H C HuangC B Pickett
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·H S ParkE J Choi
Mar 26, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ken ItohMasayuki Yamamoto
Apr 18, 2003·American Journal of Physiology. Cell Physiology·Satoshi NumazawaTakemi Yoshida

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Citations

Jul 2, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Steven O SimmonsRam Ramabhadran
Jul 10, 2016·Archives of Pharmacal Research·Sung Hyo KimSang Joon Lee
Jan 22, 2013·Biochimie·Denise Clavijo-CornejoLuis E Gómez-Quiroz

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