De novo synthesis of phospholipase A2 and prostacyclin production by proliferating rat smooth muscle cells.
We investigated the role of phospholipase A2 (PLA2) in cell cycle-dependent alterations of endogenous prostacyclin (PGI2) synthesis in aortic smooth muscle cells in culture (VSMC) from Wistar Kyoto rats. Randomly cycling VSMC generated more PGI2 than the stationary cells. Cell cycle analysis showed that PGI2 production capacity was increased from the G0/G1 through the early DNA synthetic (S) phases. Enzyme analysis revealed that, although there were different mechanisms underlying this increase in the PGI2 production during the G0/G1, the peak at 4 hours coincided with a sharp increase in PLA2 activity. This increase in PLA2 activity was preceded by an increased expression of functional PLA2 messenger RNA, and protein synthesis inhibition prevented most of the increase in PGI2 production at 4 hours. These data indicate that endogenous PGI2 generation is mainly increased during the G0/G1 period and that this event is secondary to de novo synthesis of PLA2 and probably, at least in part, to cyclooxygenase induction. This mechanism provides a negative feedback regulating VSMC proliferation.
Uehara
Y
Y
Second Department of Medicine, University of Tokyo, Japan.
Takada
S
S
Hirawa
N
N
Kawabata
Y
Y
Nagata
T
T
Numabe
A
A
Hara
H
H
Kudo
I
I
Ikeda
T
T
Inoue
K
K
D000818:Animals; D001011:Aorta; D002455:Cell Division; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000096:biosynthesis* / Q000235:genetics; D054467:Phospholipases A2; D012333:RNA, Messenger; D051381:Rats; D011921:Rats, Inbred WKY; D010738:Type C Phospholipases / Q000378:metabolism
D012333:RNA, Messenger; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D015232:Dinoprostone