Excessive endoplasmic reticulum stress induces apoptotic cell death in chronic cyclosporine A nephrotoxicity
10.3969/j.issn.1000-4718.2014.06.015
- VernacularTitle:过度内质网应激在慢性环孢素 A肾毒性细胞凋亡中的作用机制
- Author:
Wenshu QUAN
;
Yingshun JIN
;
Jizhe JIN
;
Shangguo PIAO
;
Zhenhua CUI
;
Haifeng JIN
;
Hailan ZHENG
;
Jinji LI
;
Yuji JIANG
;
Hua JIN
;
Can LI
- Publication Type:Journal Article
- Keywords:
Cyclosporine A;
Nephrotoxicity;
Endoplasmic reticulum stress;
Apoptosis
- From:
Chinese Journal of Pathophysiology
2014;(6):1047-1051
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the impact of excessive endoplasmic reticulum stress on apoptotic cell death in a rat model of chronic cyclosporine A ( CsA ) nephrotoxicity .METHODS: Male Sprague-Dawley rats on a low-salt diet were subcutaneously injected with vehicle (olive oil, 1 mL· kg-1· d-1) or CsA (15 mg/kg) daily for 1 or 4 weeks.Tu-bulointerstitial fibrosis and apoptotic cell death were estimated by trichrome staining and TUNEL staining .In addition , im-munohistochemistry and immunoblotting were used to evaluate the expression of immunoglobulin -binding protein ( BiP) , eu-karyotic initiation factor 2α(eIF2α), growth arrest and DNA damage-inducible protein 153 (GADD153), caspase-12 and caspase-3.RESULTS:The rats treated with CsA for 1 week did not develop tubulointerstitial fibrosis and TUNEL-positive cells, whereas 4-week treatment with CsA induced typical tubulointerstitial fibrosis and increased TUNEL-positive cells. CsA induced a significant increase in BiP and caspase-12 expression peaked at 1 week, and then returned to normal levels at 4 weeks.In contrast, the expression of eIF2α, GADD153 and caspase-3 in CsA-treated rat kidneys were significantly in-creased in a time-dependent manner .CONCLUSION:Excessive endoplasmic reticulum stress causes apoptotic cell death by depleting molecular chaperones and stimulating the proapoptotic pathway in chronic CsA nephrotoxicity .
