Dexamethasone decreases phospholipase C beta1 isozyme expression in human vascular smooth muscle cells.
The molecular characterization of the human PLC beta1 gene was just reported by Peruzzi et al. [Biochim. Biophys. Acta 1582 (2002) 46]. This prompted us to investigate the effects of dexamethasone on PLC beta1 expression in two types of human vascular smooth muscle cells--coronary artery smooth muscle cells (hCASMC) and aortic smooth muscle cells (hAoSMC), since glucocorticoids are known to affect the signaling pathways of Gprotein coupled receptors. Semi-quantitative RT-PCR was used to analyze mRNA expression and Western-blot for protein expression. Dexamethasone treatment in the two types of cells studied decreased (mRNA and protein) PLC beta1 isozyme expression. A rapid (2 h) fall in mRNA occurred in hCASMC after treatment, and hCASMC were more sensitive to dexamethasone (1 nM versus 100 nM) than hAoSMC. The major reduction (80%) was observed after 48 h of exposure in both VSMC. Treatment with mifeprisone, an antagonist of glucocorticoid receptors, blunted the dexamethasone effect on PLC beta1 mRNA and showed that this effect was mediated by glucocorticoids receptors.
Unité 349 de l'INSERM, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris Cedex 10, France.
Carine
C
Cueille
Stéphane
S
Frayon
Marie-Christine
MC
de Vernejoul
Jean-Michel
JM
Garel
D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D054799:Phospholipase C beta; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000502:physiology; D010738:Type C Phospholipases / Q000032:analysis / Q000096:biosynthesis*
D007527:Isoenzymes; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D010738:Type C Phospholipases; C518033:PLCB1 protein, human; D054799:Phospholipase C beta