Effects of serum from chronic renal failure rats on endoplasmic reticulum stress and activation of activating transcription factor 4 of rat arterial smooth muscle cells cultured in vitro
10.3760/cma.j.issn.1001-7097.2009.09.012
- VernacularTitle:慢性肾衰竭大鼠血清诱发主动脉平滑肌细胞内质网应激及激活转录因子4活化
- Author:
Yaoquan ZHANG
;
Bing FENG
;
Fahuan YUAN
- Publication Type:Journal Article
- Keywords:
Kidney failure;
chronic;
Serum;
Myocytes;
smooth muscle;
Endoplasmie retieulum stress;
Activating transcription factor 4
- From:
Chinese Journal of Nephrology
2009;25(9):706-710
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of the serum from chronic renal failure (CRF) rats on endoplasmic reticulum stress (ERS) and activation of activating transcription factor 4 (ATF4) of rat arterial smooth muscle cells (ASMCs) cultured in vitro and explore the possible mechanism. Methods The rat model of CRF was established by 5/6 nephrectomy. ASMCs were incubated in the media with 10% or 20% serum of CRF rats cultured in vitro. ATF4 nuclear translocation were analyzed by immunofluorescence. GRP78 (glucose regulated protein 78), p-PERK (pancreatic ER kinase) and ATF4 proteins in response to the CRF serum in ASMCs were determined by Western blot. The ATF4-DNA binding activity was analyzed by electrophoretic mobility shift assay (EMSA). Results The CRF serum could significantly promote the expression of GRP78 of ASMCs in dose-dependent manner. Under the stimulation of 20% CRF serum, nuclear translocation of ATF4 in ASMCs was found. Compared with control serum group, the expression of ATF4 and p-PERK of CRF serum group was increased significantly (P<0.01). The CRF serum could increase the ATF4-DNA binding activity. Conclusion The CRF rat serum can effectively induce ERS of ASMCs and activate the pathway of PERK-ATF4.
