NADPH oxidase-dependent signaling in endothelial cells

Role in physiology and pathophysiology

Randall S. Frey, Masuko Fukai, Asrar B. Malik

Research output: Contribution to journalReview article

254 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) including superoxide (O2 .-) and hydrogen peroxide (H2O2) are produced endogenously in response to cytokines, growth factors; G-protein coupled receptors, and shear stress in endothelial cells (ECs). ROS function as signaling molecules to mediate various biological responses such as gene expression, cell proliferation, migration, angiogenesis, apoptosis, and senescence in ECs. Signal transduction activated by ROS, "oxidant signaling," has received intense investigation. Excess amount of ROS contribute to various pathophysiologies, including endothelial dysfunction, atherosclerosis, hypertension, diabetes, and acute respiratory distress syndrome (ARDS). The major source of ROS in EC is a NADPH oxidase. The prototype phagaocytic NADPH oxidase is composed of membrane-bound gp91phox and p22hox, as well as cytosolic subunits such as p47phox, p67phox and small GTPase Rac. In ECs, in addition to all the components of phagocytic NADPH oxidases, homologues of gp91phox (Nox2) including Nox1, Nox4, and Nox5 are expressed. The aim of this review is to provide an overview of the emerging area of ROS derived from NADPH oxidase and oxidant signaling in ECs linked to physiological and pathophysiological functions. Understanding these mechanisms may provide insight into the NADPH oxidase and oxidant signaling components as potential therapeutic targets.

Original languageEnglish (US)
Pages (from-to)791-810
Number of pages20
JournalAntioxidants and Redox Signaling
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

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NADPH Oxidase
Endothelial cells
Physiology
Reactive Oxygen Species
Endothelial Cells
Oxidants
Signal transduction
Monomeric GTP-Binding Proteins
Adult Respiratory Distress Syndrome
Cell proliferation
Medical problems
G-Protein-Coupled Receptors
Gene expression
Superoxides
Hydrogen Peroxide
Cell Movement
Shear stress
Signal Transduction
Atherosclerosis
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry
  • Medicine(all)

Cite this

NADPH oxidase-dependent signaling in endothelial cells : Role in physiology and pathophysiology. / Frey, Randall S.; Fukai, Masuko; Malik, Asrar B.

In: Antioxidants and Redox Signaling, Vol. 11, No. 4, 01.04.2009, p. 791-810.

Research output: Contribution to journalReview article

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