BACKGROUND/AIMS: Apoptosis contributes to cyclosporine (CsA)-induced renal cell death. This study tested the effects of CsA-induced endoplasmic reticulum (ER) stress on apoptotic cell death in an experimental model of chronic CsA nephropathy. METHODS: CsA (15 mg/kg per day) was given to rats for 7 or 28 days. The ER stress response was evaluated with BiP expression, and the proapoptotic response was assessed with CHOP and caspase 12 expression. ER structure was evaluated by transmission electron microscopy, and apoptotic cell death was detected with TUNEL staining. RESULTS: Short-term treatment of CsA for 7 days activated both the ER stress response (induction of BiP mRNA and protein) and the proapoptotic response (upregulation of caspase 12 and CHOP mRNAs and proteins). However, long-term treatment with CsA for 28 days decreased BiP and further increased CHOP. The imbalance between the two responses coincided with the timing of the appearance of apoptotic cell death and the disruption of the ER structure. CONCLUSION: Prolonged CsA-induced ER stress causes apoptotic cell death by depleting molecular chaperones and activating the proapoptotic pathway. Copyright 2008 S. Karger AG, Basel.
BACKGROUND/AIMS: Apoptosis contributes to cyclosporine (CsA)-induced renal cell death. This study tested the effects of CsA-induced endoplasmic reticulum (ER) stress on apoptotic cell death in an experimental model of chronic CsAnephropathy. METHODS:CsA (15 mg/kg per day) was given to rats for 7 or 28 days. The ER stress response was evaluated with BiP expression, and the proapoptotic response was assessed with CHOP and caspase 12 expression. ER structure was evaluated by transmission electron microscopy, and apoptotic cell death was detected with TUNEL staining. RESULTS: Short-term treatment of CsA for 7 days activated both the ER stress response (induction of BiP mRNA and protein) and the proapoptotic response (upregulation of caspase 12 and CHOP mRNAs and proteins). However, long-term treatment with CsA for 28 days decreased BiP and further increased CHOP. The imbalance between the two responses coincided with the timing of the appearance of apoptotic cell death and the disruption of the ER structure. CONCLUSION: Prolonged CsA-induced ER stress causes apoptotic cell death by depleting molecular chaperones and activating the proapoptotic pathway. Copyright 2008 S. Karger AG, Basel.
Authors: Jin Young Kim; Jung Yeon Ghee; Sun Woo Lim; Shang Guo Piao; Byung Ha Chung; Hye Eun Yoon; Hyeon Seok Hwang; Bum Soon Choi; Jin Kim; Chul Woo Yang Journal: J Korean Med Sci Date: 2012-01-27 Impact factor: 2.153
Authors: José Sereno; Paulo Rodrigues-Santos; Helena Vala; Petronila Rocha-Pereira; Rui Alves; João Fernandes; Alice Santos-Silva; Eugénia Carvalho; Frederico Teixeira; Flávio Reis Journal: Int J Mol Sci Date: 2014-05-20 Impact factor: 5.923