Lipoprotein (a) stimulates mitogen activated protein kinase in human mesangial cells

Evidence suggests an important role of elevated serum lipoproteins in the p rogression of renal glomerulosclerosis, We report here that lipoprotein (a) (Lp(a)) increased phosphorylation and activity of mitogen activated protei n kinase (MAPK) in human mesangial cells. When protein kinase C (PKC) was d epleted by long-term incubation with the phorbol 12-O-myristate 13-acetate the effect of Lp(a) on MAPK activation was completely inhibited. Forskolin, a stimulator of the adenylyl cyclase, and dibutyryl-cAMP reduced the effec t of Lp(a) on MAPK phosphorylation and activation. We conclude that Lp(a) s timulates the MAPK cascade via activation of PKC and that activation of pro tein kinase A counteracts Lp(a) induced MAPK activation in human mesangial cells. (C) 1998 Federation of European Biochemical Societies.