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• W2149166688 endingPage "238" @default.
• W2149166688 startingPage "231" @default.
• W2149166688 abstract "Abstract The intracellular signaling mechanisms that mediate basic fibroblast growth factor (bFGF)–induced angiogenesis have not been fully identified. In particular, whether activation of the intracellular enzyme protein kinase C (PKC) is necessary or sufficient for bFGF-induced mitogenesis of human endothelial cells is not clear. Accordingly, the effect of bFGF stimulation on the Ca 2+ increase and PKC activity of normal human endothelial cells (HEC) was studied, as was the effect of inhibition of PKC and the distribution of PKC isoenzymes in these cells. The addition of bFGF to cultured HEC increased overall PKC activity in the absence of an increase in intracellular Ca 2+ and markedly stimulated their proliferation, as did the addition of PKC-activating phorbol esters. bFGF-induced proliferation was prevented by the PKC inhibitors chelerythrine and H-7 and by downregulation of PKC after prolonged incubation with phorbol esters. In contrast, these inhibitors did not prevent HEC proliferation induced by epidermal growth factor. Because of the failure of bFGF to increase Ca 2+ , we determined whether bFGF-induced proliferation could be mediated by novel or atypical PKC isoenzymes (which are not regulated by Ca 2+ ). Investigation of the isoenzyme distribution of confluent and subconfluent HEC by immunoblotting, Northern transfer analysis, and polymerase chain reaction of reverse-transcribed RNA revealed the presence of several novel and atypical isoenzymes (PKC-δ, -η, -θ, and -ζ) as well as small amounts of the conventional (Ca 2+ -regulated) isoenzymes PKC-α and -β. Activation of PKC by bFGF, in the absence of an increase in intracellular Ca 2+ , suggests that one or more of these Ca 2+ -independent PKC isoenzymes are both necessary and sufficient for HEC proliferation after bFGF." @default.
• W2149166688 created "2016-06-24" @default.
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• W2149166688 date "1995-08-01" @default.
• W2149166688 modified "2023-09-25" @default.
• W2149166688 title "Requirement for Protein Kinase C Activation in Basic Fibroblast Growth Factor–Induced Human Endothelial Cell Proliferation" @default.
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• W2149166688 doi "https://doi.org/10.1161/01.res.77.2.231" @default.
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• W2149166688 hasPublicationYear "1995" @default.
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