Oxidized LDL induces transcription factor activator protein-1 in rat mesangial cells.
Cell Biochem Funct
; 21(3): 249-56, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-12910478
ABSTRACT
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 microg 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 microg 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.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Ligação a DNA
/
Mesângio Glomerular
/
Lipoproteínas LDL
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Biochem Funct
Ano de publicação:
2003
Tipo de documento:
Article