Signal pathways involve in the stimulation of AP-1 binding activity induced by ox-LDL in mcsangial cells
- VernacularTitle:氧化-低密度脂蛋白诱导系膜细胞转录激活蛋白1活化的信号转导通路
- Author:
Yuancheng WANG
;
Zhaolong WU
;
Qin ZHOU
- Publication Type:Journal Article
- Keywords:
Low density lipoprotein;
Activator protein-1;
Protein kinases;
Mesangial cells
- From:
Chinese Journal of Nephrology
1994;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the possible role of protein kinase(PK) activity in the induction of AP-1 by ox-LDL in mesangial cells and to elucidate the upstream signal pathways involved in the ox-LDL-induced AP-1 binding. Methods Rat mesangial cells were randomly divided into the normal cells, ox-LDL-treated cells and PK inhibitor + ox-LDL-treated cells. Treatments with the PKC inhibitor bisindolylmaleimide I, the PKA inhibitor H89, the PTK inhibitor genistein (GEN), the MEKi inhibitor PD98059, or the p38 MAPK inhibitor SB203580 were applied prior to a 24-hour incubation of ox-LDL in mesangial cells. The phosphorylation of MAPK families was detected by Weatern blot analysis. AP-1 binding was determined by gel shift assay. Results Ox-LDL stimulated the phosphorylation of JNKi/SAPK and p38 MAPK( P 0. 05) . Bisindolylmaleimide I at 50, 100, 200 nmol/L appreciably reduced the ox-LDL-induced AP-1 binding. H89 at 0. 5, 5 umol/L significantly inhibited AP-1 binding by ox-LDL. GEN at 25, 50 umol/L did not reduce the AP-1 binding by ox-LDL, but when GEN rose up to 100 umol/L, the ox-LDL-induced AP-1 binding significantly decreased in mesangial cells. However, SB203580 and PD98059 did not reduce the ox-LDL-induced AP-1 binding in the present study. Conclusion Multiple protein kinases may involve in the stimulation of AP-1 by ox-LDL in mesangial cells.