Phospholipase D is involved in oxidative stress-induced migration of vascular smooth muscle cells via tyrosine phosphorylation and protein kinase C.
- Author:
Joonmo KIM
1
;
Gyesik MIN
;
Young Seuk BAE
;
Do Sik MIN
Author Information
1. Department of Physiology, College of Medicine, The Catholic University, Seoul 137-701, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
migration;
PKC;
PLD;
tyrosine phosphorylation
- MeSH:
Animals;
Cell Movement/drug effects/*physiology;
Cells, Cultured;
Enzyme Activation/drug effects;
Enzyme Inhibitors/pharmacology;
Genistein/pharmacology;
Hydrogen Peroxide/pharmacology;
Muscle, Smooth, Vascular/cytology/*physiology;
*Oxidative Stress/drug effects;
Phospholipase D/*metabolism;
Phosphorylation/drug effects;
Protein Kinase C/*metabolism;
Protein-Tyrosine Kinase/antagonists & inhibitors;
Rats;
Rats, Sprague-Dawley;
Research Support, Non-U.S. Gov't;
Signal Transduction/drug effects;
Vanadates/pharmacology;
Vascular Diseases/metabolism
- From:Experimental & Molecular Medicine
2004;36(2):103-109
- CountryRepublic of Korea
- Language:English
-
Abstract:
Oxidative stress has been implicated in mediation of vascular disorders. In the presence of vanadate, H2O2 induced tyrosine phosphorylation of PLD1, protein kinase C-a (PKC-a), and other unidentified proteins in rat vascular smooth muscle cells (VSMCs). Interestingly, PLD1 was found to be constitutively associated with PKC-a in VSMCs. Stimulation of the cells by H2O2 and vanadate showed a concentration-dependent tyrosine phosphorylation of the proteins in PLD1 immunoprecipitates and activation of PLD. Pretreatment of the cells with the protein tyrosine kinase inhibitor, genistein resulted in a dose-dependent inhibition of H2O2-induced PLD activation. PKC inhibitor and down-regulation of PKC abolished H2O2-stimulated PLD activation. The cells stimulated by oxidative stress (H2O2) caused increased cell migration. This effect was prevented by the pretreatment of cells with tyrosine kinase inhibitors, PKC inhibitors, and 1-butanol, but not 3-butanol. Taken together, these results suggest that PLD might be involved in oxidative stress-induced migration of VSMCs, possibly via tyrosine phosphorylation and PKC activation.
