Lipoprotein (a) stimulates mitogen activated protein kinase in human mesangial cells.
Evidence suggests an important role of elevated serum lipoproteins in the progression of renal glomerulosclerosis. We report here that lipoprotein (a) (Lp(a)) increased phosphorylation and activity of mitogen activated protein kinase (MAPK) in human mesangial cells. When protein kinase C (PKC) was depleted 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 effect of Lp(a) on MAPK phosphorylation and activation. We conclude that Lp(a) stimulates the MAPK cascade via activation of PKC and that activation of protein kinase A counteracts Lp(a) induced MAPK activation in human mesangial cells.
Mondorf
U F
UF
Division of Nephrology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. mondorf@em.uni-frankfurt.de
Piiper
A
A
Herrero
M
M
Bender
M
M
Scheuermann
E H
EH
Geiger
H
H
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
D017270:Lipoprotein(a); D000242:Cyclic AMP; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases