Characteristics and actions of NAD(P)H oxidase on the sarcoplasmic reticulum of coronary artery smooth muscle

Abstract

. Characteristics and actions of NAD(P)H oxidase on the sarcoplasmic reticulum of coronary artery smooth muscle.

Local production of O2− by NAD(P)H oxidase in the sarcoplasmic reticulum of coronary arterial myocytes: cADPR-mediated Ca2+ regulation

“…We have recently reported that mNOX in VSMCs produced O 2 .− in autocrine or paracrine producing manner when the cells were exposed to different agonists [7]. Using purified sarcoplasmic reticulum (SR) from coronary arterial myocytes (CAMs), we also demonstrated that an NOX is present on the SR, and this oxidase locally activates the cyclic ADP -ribose (cADPR) -sensitive ryanodine receptors/Ca 2+ (RyR/ Ca 2+ ) release channels [3]. cADPR is a novel Ca 2+ mobilizing second messenger, which is capable of inducing Ca 2+ release from the SR via activation of RyR in CAMs [8][9][10][11][12].…”

“…NAD(P)H oxidase (NOX) has been reported to be one of major sources of reactive oxygen species (ROS) in the vasculature [1][2][3]. This vascular redox regulatory enzyme is of characteristics of phagocyte NOX, which is composed of two transmembrane-bounded catalytic proteins of gp91 phox and p22 phox , and three cytosol-associated subunits of p47 phox , p67 phox and p40 phox .…”

“…This vascular redox regulatory enzyme is of characteristics of phagocyte NOX, which is composed of two transmembrane-bounded catalytic proteins of gp91 phox and p22 phox , and three cytosol-associated subunits of p47 phox , p67 phox and p40 phox . In addition to gp91 phox named as Nox2, some other homologues of gp91 phox such as Nox1, Nox4 and Nox5 were identified in the vascular cells such as endothelial and smooth muscle cells [3,4]. NOX is now well accepted as an important enzyme that produces O 2 .− in the vasculature under physiological and pathological conditions to exert redox regulatory action on vascular function or to produce pathogenic responses.…”

“…In vascular smooth muscle cells (VSMCs), many studies have demonstrated that O 2 .− is accumulated when NOX is activated [1][2][3]. This intracellular accumulation of O 2 .− led to an assumption that a plasma membrane-bound NOX may produce and release O 2 .− into cells, which is different from the orientation of phagocyte NOX [1].…”

“…However, the topologic analysis has indicated that membrane-associated NOX should not release O 2 .− into cytosol [5]. Recent studies on subcellular localization of vascular NOX have also demonstrated that O 2 .− within VSMCs may not be derived from plasma membrane NOX (mNOX), but rather from intracellular compartmental NOXs [3,6,7]. We have recently reported that mNOX in VSMCs produced O 2 .− in autocrine or paracrine producing manner when the cells were exposed to different agonists [7].…”