Staurosporine stimulates phospholipase D activation in human polymorphonuclear leukocytes.
Treatment of 1-O-[3H]alkyl-2-acyl-phosphatidylcholine-prelabeled human polymorphonuclear leukocytes (PMNs) with staurosporine (50 nM to 1 microM) induced a time- and concentration-dependent generation of tritiated phosphatidic acid (PA), reaching approximately 225% of the control value at 15-20 min. In the presence of ethanol, staurosporine induced a production of phosphatidylethanol (PEt) reaching, 250% of control values, and partial inhibition of PA production, consistent with PLD activation. The amount of ether-linked acylglycerol (EAG) was weakly enhanced (29%) after 5 min of PMN treatment; longer treatment resulted in no significant EAG production, suggesting a possible late inhibition of PA hydrolase activity. Staurosporine concentrations that induced an elevation in PA completely depressed protein kinase C (PKC) activity in both soluble and particulate cell fractions, suggesting that PLD activation may occur independently from PKC activation. PLD may thus represent a potential cellular target for staurosporine action.
Périanin
A
A
Département de Pharmacologie, CNRS URA 595, Hôpital Cochin, Paris, France.
Combadière
C
C
Pedruzzi
E
E
Djerdjouri
B
B
Hakim
J
J
D000470:Alkaloids / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020404:Glycerophospholipids; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000201:enzymology*; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine
D000470:Alkaloids; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; C051521:phosphatidylethanol; D011493:Protein Kinase C; D010739:Phospholipase D; D019311:Staurosporine