Release of cytochrome c and activation of caspases related to myocyte apoptosis in obstructed ureters in a rat model of obstructive uropathy.

Abstract

To investigate the roles of cytochrome c and caspases in the pathogenesis of muscular damage in obstructed ureters in a rat model. Apoptotic cells were detected using in situ end-labelling of DNA fragments. The expression of cytochrome c, and caspases-3, -8 and -9 was examined in 54 rats, using immunohistochemistry. The severity of ureteric smooth muscle damage increased during obstruction. Apoptotic myocytes, and the expression of cytochrome c and the three caspases in the smooth muscle layer were apparent 14 days after ligation, reaching a peak at 21 days. The numbers of apoptotic cells in the smooth muscle layer correlated significantly with expression of cytochrome c and the three caspases (r = 0.8673, 0.8701, 0.5723 and 0.7910, respectively; all P < 0.01). The expression of cytochrome c in the smooth muscle layer correlated significantly with the expression of the three caspases (r = 0.8234, 0.7558 and 0.7825, respectively; all P < 0.001). The expression of caspase-3 and -8, and -3 and -9 also correlated significantly (r = 0.6721 and 0.8501, respectively; both P < 0.002). Cytochrome c and caspases are involved in ureteric myocyte apoptosis; the release of cytochrome c might be important in ureteric damage during obstructive uropathy.