Excessive endoplasmic reticulum stress induces apoptotic cell death in chronic cyclosporine A nephrotoxicity / 中国病理生理杂志
Chinese Journal of Pathophysiology
; (12): 1047-1051, 2014.
Article
en Zh
| WPRIM
| ID: wpr-451806
Biblioteca responsable:
WPRO
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 .
Texto completo:
1
Banco de datos:
WPRIM
Tipo de estudio:
Prognostic_studies
Idioma:
Zh
Año:
2014
Tipo del documento:
Article