Exp Mol Med.  2004 Apr;36(2):103-109.

Phospholipase D is involved in oxidative stress-induced migration of vascular smooth muscle cells via tyrosine phosphorylation and protein kinase C

• Kim J
• Min G
• Bae YS
• Min DS

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.

Keyword

migration; PKC; PLD; tyrosine phosphorylation

MeSH Terms

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