Atherogenic lipoproteins stimulate mesangial cell p42 mitogen-activated protein kinase.
Previously, it has been shown that atherogenic lipoproteins, through the activation of glomerular cells, stimulate pathobiological processes involved in monocyte infiltration into the mesangium. This study examined the role of LDL and its oxidatively modified variants (mildly oxidatively modified LDL [mm-LDL] and oxidatively modified LDL [ox-LDL]) on the activation of mesangial cell p42 mitogen-activated protein kinase (MAP kinase), a key intracellular signaling mechanism associated with cell proliferation. The incubation of mesangial cells with either LDL, mm-LDL, or ox-LDL induced the activation of MAP kinase dose dependently. The activation of MAP kinase by these lipoproteins in mesangial cells occurred biphasically: initially at 15 min of incubation period and at later time points of 8 to 24 h. No activation of MAP kinase was noted between 30 min (except in LDL) and 6 h. The induction of MAP kinase by both mm-LDL and ox-LDL was greater by 1.5- to 2-fold when compared with LDL. Similarly, these atherogenic lipoproteins stimulated mesangial cell proliferation. Lysophosphatidylcholine, a component of both oxidatively modified variants of LDL, markedly stimulated mesangial cell MAP kinase activity at early incubation times (5 to 30 min) but not at later time points (3 to 24 h), suggesting that lysophosphatidylcholine may, at least in part but not solely, act as an active component of ox-LDL-mediated effects. These data define putative key signal transduction events associated with lipoprotein-mediated induction of mesangial cell proliferation.
Bassa
B V
BV
Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Roh
D D
DD
Kirschenbaum
M A
MA
Kamanna
V S
VS
D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011233:Precipitin Tests; D013997:Time Factors
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010982:Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1