ANG II stimulates phospholipase D through PKCzeta activation in VSMC: implications in adhesion, spreading, and hypertrophy
Parmentier, JH; Pavicevic, Z; Malik, KU
HERO ID
1071213
Reference Type
Journal Article
Year
2006
Language
English
PMID
| HERO ID | 1071213 |
|---|---|
| In Press | No |
| Year | 2006 |
| Title | ANG II stimulates phospholipase D through PKCzeta activation in VSMC: implications in adhesion, spreading, and hypertrophy |
| Authors | Parmentier, JH; Pavicevic, Z; Malik, KU |
| Journal | American Journal of Physiology: Heart and Circulatory Physiology |
| Volume | 290 |
| Issue | 1 |
| Page Numbers | H46-H54 |
| Abstract | ANG II stimulates phospholipase D (PLD) activity and growth of vascular smooth muscle cells (VSMC). The atypical protein kinase C-zeta (PKCzeta) 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 PKCzeta and PLD and their implication in VSMC adhesion, spreading, and hypertrophy. ANG II stimulated PKCzeta activity with maximal activation at 30 s followed by a decline in its activity to 45% above basal at 5 min. Inhibition of PKCzeta activity with a myristoylated pseudosubstrate peptide or overexpression of a kinase-inactive form of PKCzeta decreased ANG II-induced PLD activity. Moreover, depletion of PKCzeta with selective antisense oligonucleotides also decreased ANG II-induced PLD activity. Interaction between PLD2 and PKCzeta 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 PKCzeta and PLD2 in VSMC adhesion, spreading, and hypertrophy was investigated. Inhibition of PKCzeta and PLD2 activity or expression attenuated VSMC adhesion to collagen I and ANG II-induced cell spreading and hypertrophy. These results demonstrate that ANG II-induced PLD activation is regulated by PKCzeta and suggest a crucial role of PKCzeta-dependent PLD2 in VSMC functions such as adhesion, spreading, and hypertrophy, which are associated with the pathogenesis of atherosclerosis and malignant hypertension. |
| Doi | 10.1152/ajpheart.00769.2005 |
| Pmid | 16113073 |
| Wosid | WOS:000234148200005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000234148200005 |
| Is Public | Yes |
| Language Text | English |
| Keyword | vascular smooth muscle cells; protein kinase C zeta; angiotensin II |
| Is Qa | No |