Modulation of phospholipase A2 lytic activity by actin and myosin.
Prostacyclin (PGI2) production is closely coupled with endothelial cell shape and F-actin distribution in vitro. These findings may implicate cytoskeletal constituents in a mechanism regulating eicosanoid metabolism. To determine the potential for such a regulatory mechanism, cytoskeletal protein effects on the rate-limiting eicosanoid cascade enzyme (phospholipase A2; PLA2) were studied. Membrane phospholipid degradation was indirectly determined by spectrophotometric measurement of PLA2-induced rat red blood cell ghost (RBC-G) hemolysis. PLA2 was incubated with actin (skeletal, smooth, or nonmuscle cell) at a nonmuscle cell concentration (100 microM) and then exposed to the RBC-G. Comparisons in the presence or absence of actin revealed that F-actin stimulated whereas G-actin suppressed PLA2 lytic behavior significantly (P less than 0.05). When a 10: or 100:1 F-actin to myosin ratio was used, the F-actin stimulatory effect was significantly (P less than 0.05) reduced. These findings suggest that the in vitro correlation between PGI2 production and endothelial cell shape may be the result of PLA2 regulation by cytoskeletal elements that impart cellular form.
Dubose
D A
DA
US Army Research Institute of Environmental Medicine, Natick, Massachusetts 01760.
Shepro
D
D
Hechtman
H B
HB
D000199:Actins / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D009218:Myosins / Q000494:pharmacology*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats
D000199:Actins; D011464:Epoprostenol; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D009218:Myosins