{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:11:35Z","timestamp":1770358295559,"version":"3.49.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,7,1]]},"abstract":"<jats:p>In addition to the well-documented role of nitric oxide (NO) as a vasodilator, NO has also been implicated in vascular smooth muscle cell (VSMC) growth arrest. Signaling mechanisms responsible for growth factor receptor-mediated VSMC proliferation include the extracellular signal-regulated kinase (ERK) and possibly the protein kinase B (PKB) cascade. Thus the present study was designed to test the hypothesis that, in A7r5 vascular smooth muscle-derived cells, platelet-derived growth factor (PDGF)-induced activation of either ERK or PKB is regulated by NO, which then modulates cellular proliferation and\/or apoptosis. PKB-\u03b1 was the predominant isoform of PKB expressed in A7r5 cells and was also expressed in rabbit carotid arteries and aortae. Phosphorylation of PKB-\u03b1 and ERK induced by PDGF-BB was maximal within 5\u201315 min in A7r5 cells. Preincubation of A7r5 cells with the NO donor S-nitroso- N-acetylpenicillamine (SNAP) resulted in a biphasic regulation of PDGF-stimulated PKB-\u03b1 phosphorylation and bioactivity. Acute exposure to SNAP significantly augmented PDGF-induced activation of PKB-\u03b1, whereas prolonged incubation led to a marked diminution in PDGF-induced activation of PKB-\u03b1. In contrast, SNAP did not affect PDGF-induced activation of ERK at any time point. The cGMP-independent effects of SNAP on PDGF-induced activation of PKB-\u03b1 were established with the use of an inhibitor of soluble guanylyl cyclase, ODQ, as well as a cell-permeable analog of cGMP, 8-bromo-cGMP. Prolonged treatment of A7r5 cells with SNAP led to a significant decrease in DNA synthesis without an appreciable increase in apoptosis. These data suggest that, after prolonged exposure to SNAP, NO selectively attenuates PDGF-induced increase in PKB-\u03b1 activation, which in turn may contribute to diminished VSMC proliferation by mechanisms involving growth arrest but not apoptosis.<\/jats:p>","DOI":"10.1152\/ajpcell.2000.279.1.c225","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:52:46Z","timestamp":1514155966000},"page":"C225-C235","source":"Crossref","is-referenced-by-count":33,"title":["NO regulates PDGF-induced activation of PKB but not ERK in A7r5 cells: implications for vascular growth arrest"],"prefix":"10.1152","volume":"279","author":[{"given":"Lakshman","family":"Sandirasegarane","sequence":"first","affiliation":[{"name":"Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 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