{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:38:50Z","timestamp":1791113930224,"version":"4.1.0"},"reference-count":35,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>An increase in intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in pulmonary arterial smooth muscle cells (PASMCs) induces hypoxic cellular responses in the lungs; however, the underlying molecular mechanisms remain incompletely understood. We report, for the first time, that acute hypoxia significantly enhances phospholipase C (PLC) activity in mouse resistance pulmonary arteries (PAs), but not in mesenteric arteries. Western blot analysis and immunofluorescence staining reveal the expression of PLC-\u03b31 protein in PAs and PASMCs, respectively. The activity of PLC-\u03b31 is also augmented in PASMCs following hypoxia. Lentiviral shRNA-mediated gene knockdown of mitochondrial complex III Rieske iron-sulfur protein (RISP) to inhibit reactive oxygen species (ROS) production prevents hypoxia from increasing PLC-\u03b31 activity in PASMCs. Myxothiazol, a mitochondrial complex III inhibitor, reduces the hypoxic response as well. The PLC inhibitor U73122, but not its inactive analog U73433, attenuates the hypoxic vasoconstriction in PAs and hypoxic increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in PASMCs. PLC-\u03b31 knockdown suppresses its protein expression and the hypoxic increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Hypoxia remarkably increases inositol 1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>) production, which is blocked by U73122. The IP<jats:sub>3<\/jats:sub>receptor (IP<jats:sub>3<\/jats:sub>R) antagonist 2-aminoethoxydiphenyl borate (2-APB) or xestospongin-C inhibits the hypoxic increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. PLC-\u03b31 knockdown or U73122 reduces H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in PASMCs and contraction in PAs. 2-APB and xestospongin-C produce similar inhibitory effects. In conclusion, our findings provide novel evidence that hypoxia activates PLC-\u03b31 by increasing RISP-dependent mitochondrial ROS production in the complex III, which causes IP<jats:sub>3<\/jats:sub>production, IP<jats:sub>3<\/jats:sub>R opening, and Ca<jats:sup>2+<\/jats:sup>release, playing an important role in hypoxic Ca<jats:sup>2+<\/jats:sup>and contractile responses in PASMCs.<\/jats:p>","DOI":"10.1152\/ajplung.00310.2012","type":"journal-article","created":{"date-parts":[[2012,12,2]],"date-time":"2012-12-02T01:34:33Z","timestamp":1354412073000},"page":"L143-L151","source":"Crossref","is-referenced-by-count":36,"title":["Important role of PLC-\u03b31 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells"],"prefix":"10.1152","volume":"304","author":[{"given":"Vishal R.","family":"Yadav","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Sciences, Albany Medical College, Albany, New 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