Novel gp91 <sup> <i>phox</i> </sup> Homologues in Vascular Smooth Muscle Cells

DOI Web Site 24 Citations
  • Bernard Lassègue
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • Dan Sorescu
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • Katalin Szöcs
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • QiQin Yin
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • Marjorie Akers
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • Yong Zhang
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • Sharon L. Grant
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • J. David Lambeth
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.
  • Kathy K. Griendling
    From the Department of Medicine, Division of Cardiology (B.L., D.S., K.S., Q.Q.Y., M.A., Y.Z., S.L.G., K.K.G.) and Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga.

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Other Title
  • nox1 Mediates Angiotensin II–Induced Superoxide Formation and Redox-Sensitive Signaling Pathways

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Abstract

<jats:p> <jats:italic>Abstract</jats:italic> —Emerging evidence indicates that reactive oxygen species are important regulators of vascular function. Although NAD(P)H oxidases have been implicated as major sources of superoxide in the vessel wall, the molecular identity of these proteins remains unclear. We recently cloned nox1 (formerly mox-1), a member of a new family of gp91 <jats:sup> <jats:italic>phox</jats:italic> </jats:sup> homologues, and showed that it is expressed in proliferating vascular smooth muscle cells (VSMCs). In this study, we examined the expression of three nox family members, nox1, nox4, and gp91 <jats:sup> <jats:italic>phox</jats:italic> </jats:sup> , in VSMCs, their regulation by angiotensin II (Ang II), and their role in redox-sensitive signaling. We found that both nox1 and nox4 are expressed to a much higher degree than gp91 <jats:sup>phox</jats:sup> in VSMCs. Although serum, platelet-derived growth factor (PDGF), and Ang II downregulated nox4, they markedly upregulated nox1, suggesting that this enzyme may account for the delayed phase of superoxide production in these cells. Furthermore, an adenovirus expressing antisense nox1 mRNA completely inhibited the early phase of superoxide production induced by Ang II or PDGF and significantly decreased activation of the redox-sensitive signaling molecules p38 mitogen-activated protein kinase and Akt by Ang II. In contrast, redox-independent pathways induced by PDGF or Ang II were unaffected. These data support a role for nox1 in redox signaling in VSMCs and provide insight into the molecular identity of the VSMC NAD(P)H oxidase and its potentially critical role in vascular disease. </jats:p>

Journal

  • Circulation Research

    Circulation Research 88 (9), 888-894, 2001-05-11

    Ovid Technologies (Wolters Kluwer Health)

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