Exp Mol Med.  2002 Mar;34(1):38-46.

The p38 mitogen-activated protein kinase is involved in stress-induced phospholipase D activation in vascular smooth muscle cells

• Min DS
• Shin EY
• Kim EG

Abstract

Oxidative stress has been implicated in mediation of vascular disorders. Earlier study showed that the exposure of vascular smooth muscle cells (VSMC) to pervanadate (hydrogen peroxide plus orthovanadate) resulted in the accumulation of [3H]phosphatidylbutanol. In this study, the effect of pervanadate on the activation of p38 mitogen-activated protein kinase (p38 MAPK) was studied in the VSMC. Pervanadate treatment activated p38 MAPK in a dose-and time-dependent manner. Interestingly, specific inhibition of p38 MAPK with SB203580 attenuated pervanadate-induced PLD activation. This correlates with the finding that expression of dominant negative mutants of MKK3/6 inhibited the PLD activation. SB203580 pretreatment also inhibited other cellular stressors (i.e. high osmolarity and UV light)-induced PLD activation. The possible correlationship of p38 MAPK activation with PKC was examined since PKC is reported to be involved in the pervanadate-induced PLD activation. Calphostin C, a PKC inhibitor, suppressed pervanadate-induced p38 MAPK and PLD activation in a dose-dependent manner. These results suggest that PKC-p38 MAPK may represent an upstream pathway of PLD in the signal transduction of cellular stress.

MeSH Terms

Animal
Ca(2+)-Calmodulin Dependent Protein Kinase/genetics/metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors/pharmacology
Imidazoles/pharmacology
MAP Kinase Signaling System/physiology
Mannitol/pharmacology
Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
Muscle, Smooth, Vascular/cytology/drug effects/*metabolism
*Oxidative Stress
Phospholipase D/*metabolism
Protein Kinase C/antagonists & inhibitors/metabolism
Pyridines/pharmacology
Rats
Rats, Sprague-Dawley
Tetradecanoylphorbol Acetate/pharmacology
Time Factors
Vanadates/pharmacology