Mechanism of angiotensin II-induced superoxide production in cells reconstituted with angiotensin type 1 receptor and the components of NADPH oxidase

Hyun Choi, Thomas L. Leto, László Hunyady, Kevin J. Catt, Soo Bae Yun, Goo Rhee Sue

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The mechanism of angiotensin II (Ang II)-induced superoxide production was investigated with HEK293 or Chinese hamster ovary cells reconstituted with the angiotensin type 1 receptor (AT1R) and NADPH oxidase (either Nox1 or Nox2) along with a pair of adaptor subunits (either NOXO1 with NOXA1 or p47phox with p67phox). Ang II enhanced the activity of both Nox1 and Nox2 supported by either adaptor pair, with more effective activation of Nox1 in the presence of NOXO1 and NOXA1 and of Nox2 in the presence of p47phox and p67phox. Expression of several AT1R mutants showed that interaction of the receptor with G proteins but not that with β-arrestin or with other proteins (Jak2, phospholipase C-γ1, SH2 domain-containing phosphatase 2) that bind to the COOH-terminal region of AT1R, was necessary for Ang II-induced superoxide production. The effects of constitutively active α subunits of G proteins and of various pharmacological agents implicated signaling by a pathway comprising AT 1R, Gαq/11, phospholipase C-β, and protein kinase C as largely, but not exclusively, responsible for Ang II-induced activation of Nox1 and Nox2 in the reconstituted cells. A contribution of Gα12/13, phospholipase D, and phosphatidylinositol 3-kinase to Ang II-induced superoxide generation was also suggested, whereas Src and the epidermal growth factor receptor did not appear to participate in this effect of Ang II. In reconstituted cells stimulated with Ang II, Nox2 exhibited a more sensitive response than Nox1 to the perturbation of protein kinase C, phosphatidylinositol 3-kinase, or the small GTPase Rac1.

Original languageEnglish
Pages (from-to)255-267
Number of pages13
JournalJournal of Biological Chemistry
Volume283
Issue number1
DOIs
Publication statusPublished - Jan 4 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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