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Oxidized LDL induces transcription factor activator protein‐1 in rat mesangial cells
Author(s) -
Wu ZhaoLong,
Wang YuanCheng,
Zhou Qin,
Ge YuQiang,
Lan Yang
Publication year - 2003
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1015
Subject(s) - activator (genetics) , chemistry , mesangial cell , microbiology and biotechnology , transcription factor , medicine , endocrinology , biochemistry , biology , receptor , gene , in vitro
It has been shown that oxidized low‐density lipoprotein (ox‐LDL), through the activation of glomerular cells, stimulates pathobiological processes involved in monocyte infiltration into the mesangium. The underlying molecular mechanisms are not fully understood. The present study showed that ox‐LDL strongly induced AP‐1 binding activity in rat mesangial cells (RMCs) in a dose‐ and time‐dependent manner, reaching the maximal activation at 250 μg ml −1 within 24 h. The results from mobility shift assays and Western blotting analysis revealed that this AP‐1 binding increase involved c‐Jun, but not c‐Fos. Moreover, this ox‐LDL‐increased AP‐1 binding was inhibited by several protein kinase (PK) inhibitors: the protein kinase C (PKC) inhibitor Bisindolylmaleimide I, the cAMP‐dependent PK (PKA) inhibitor H89, and the tyrosine PK (PTK) inhibitor genistein. Protein phosphorylation represents mitogen‐activated protein kinase (MAPK) activity. Therefore, we examined the role of ox‐LDL on the activation of mesangial cell JNK/SAPK, the only recognized protein kinase that catalyses phosphorylation of c‐Jun. The incubation of mesangial cells with ox‐LDL induced phosphorylation of JNK1/SAPK dose dependently, with the maximal response at 150 μg ml −1 . This study demonstrates that multiple kinase activities are involved in the mechanism of ox‐LDL‐induced AP‐1 activation in mesangial cells, and ox‐LDL stimulates AP‐1 through JNK‐c‐Jun other than MEK‐c‐Fos signalling pathway. Copyright © 2003 John Wiley & Sons, Ltd.