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- W1982877488 abstract "Protein kinase G (PKG), a recognized downstream mediator of nitric oxide, is a key regulator of cardiovascular physiology and pathology. High-level stimulation of cyclic guanosine monophosphate/PKG signaling using high concentrations of nitric oxide donors, mimicking pathological conditions, induces apoptosis in vascular smooth muscle cells. In contrast, we have found that PKG at basal and moderately elevated activity prevents both spontaneous and toxin-induced apoptosis in many other cells. We hypothesized that PKG's apoptosis-regulatory role in vascular smooth muscle cells depends on PKG activation levels [low/basal-level activation prevents apoptosis, whereas high-level activation (hyperactivation) causes apoptosis]. Furthermore, we hypothesized that, although PKG hyperactivation inhibits vascular smooth muscle cell proliferation (potentially causing anti-atherogenic effects), basal PKG activity may promote vascular smooth muscle cell proliferation/atherogenesis. Involvement of PKG in apoptosis and proliferation was determined in unpassaged vascular smooth muscle cells from mouse aorta. Western blot analysis was used to determine PKG expression, and activators/inhibitors of PKG activity were used to determine involvement in apoptosis (Hoechst staining and DNA-fragmentation ELISAs) and proliferation (cell count, MTT assay, and BrdU incorporation). Both PKG-Iα and PKG-Iβ isoforms were expressed. Lower-level stimulation of PKG using the nitric oxide donor S-nitroso-acetylpenacillamine (10, 50 μM) significantly (P<.05) lowered spontaneous apoptosis, whereas S-nitroso-acetylpenacillamine at higher concentrations (500, 1000 μM) elevated apoptosis. Twenty-four-hour pretreatment with atrial natriuretic peptide, a PKG activator, completely prevented high-concentration, nitric oxide-induced apoptosis. Inhibition of basal PKG activity using highly selective PKG inhibitors, DT-2 and DT-3, significantly (P<.001) increased apoptosis and inhibited DNA synthesis/proliferation. The data suggest that basal/moderately elevated PKG activity protects against high/pathological-level nitric oxide-induced apoptosis and promotes DNA synthesis/proliferation in vascular smooth muscle cells, potentially important for atherogenesis." @default.
- W1982877488 created "2016-06-24" @default.
- W1982877488 creator A5057388371 @default.
- W1982877488 creator A5076993163 @default.
- W1982877488 date "2010-11-01" @default.
- W1982877488 modified "2023-10-10" @default.
- W1982877488 title "Protein kinase G activity prevents pathological-level nitric oxide-induced apoptosis and promotes DNA synthesis/cell proliferation in vascular smooth muscle cells" @default.
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- W1982877488 doi "https://doi.org/10.1016/j.carpath.2009.11.001" @default.
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