Prolonged Endoplasmic Reticulum Stress Induces Apoptotic Cell Death in an Experimental Model of Chronic Cyclosporine NephropathyHan S.W. · Li C. · Ahn K.O. · Lim S.W. · Song H.G. · Jang Y.S. · Cho Y.M. · Jang Y.M. · Ghee J.Y. · Kim J.Y. · Kim S.H. · Kim J. · Kwon O.J. · Yang C.W.
aDivision of Nephrology, Department of Internal Medicine, bDepartment of Biochemistry, and cCell Death Research Center, Department of Anatomy, The Catholic University of Korea, Seoul, South Korea; dDepartment of Internal Medicine, The Affiliated Hospital, Yanbian University Medical College, Yanji, PR China
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.
|Direct payment||This item at the regular price: USD 38.00|
|Payment from account||With a Karger Pay-per-View account (down payment USD 150)
you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50