| Autor: |
Parmentier, Jean-Hugues, Pavicevic, Zoran, Malik, Kafait U. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Jan2006, Vol. 290 Issue 1, pH46-H54, 9p, 2 Charts, 13 Graphs |
| Abstrakt: |
ANG II stimulates phospholipase D (PLD) activity and growth of vascular smooth muscle cells (VSMC). The atypical protein kinase C-ζ (PKCζ) plays a central role in the regulation of cell survival and proliferation. This study was conducted to determine the relationship between ANG II-induced activation of PKCζ and PLD and their implication in VSMC adhesion, spreading, and hypertrophy. ANG II stimulated PKCζ activity with maximal activation at 30 s followed by a decline in its activity to 45% above basal at 5 mm. Inhibition of PKCζ activity with a myristoylated pseudosubstrate peptide or overexpression of a kinase-inactive form of PKCζ decreased ANG II-induced PLD activity. Moreover, depletion of PKCζ with selective antisense oligonucleotides also decreased ANG II-induced PLD activity. Interaction between PLD2 and PKCζ in VSMC was detected by coimmunoprecipitation. ANG II-induced PLD activity was inhibited by the primary alcohol n-butanol but not the tertiary alcohol t-butanol. The functional significance of PKCζ and PLD2 in VSMC adhesion, spreading, and hypertrophy was investigated. Inhibition of PKCζ and PLD2 activity or expression attenuated VSMC adhesion to collagen I and ANG lI-induced cell spreading and hypertrophy. These results demonstrate that ANG II-induced PLD activation is regulated by PKCζ and suggest a crucial role of PKCζ-dependent PLD2 in VSMC functions such as adhesion, spreading, and hypertrophy, which are associated with the pathogenesis of atherosclerosis and malignant hypertension. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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