Over-expression of apoptosis-related proteins contributes to muscular damage in the obstructed ureter of the rat

Abstract

Objective To determine the role of apoptosis-related proteins (Myc, Bax, Bcl-2, and Bcl-X L ) in muscular damage in obstructed rat ureters. Materials and methods The in situ end-labelling of DNA fragments and the expression of apoptosis-related proteins were assessed, using immunohistochemistry, in 54 female Sprague-Dawley rats in which unilateral ureteric obstruction was caused by ureteric ligation. Results The severity of ureteric damage increased during the period of obstruction. Apoptotic cells and the expression of Bax were detected in the smooth muscle layer from 14 days after ligation. The percentage of apoptotic cells and the expression of Bax in the smooth muscle layer increased and reached a peak 21 days after ligation, and then declined. The expression of Myc was also detected in the smooth muscle layer 14 days after ligation but reached a peak at 28 days. The expressions of Bcl-2 and Bcl-X L in the smooth muscle layer were only detected 21 and 28 days after ligation. The numbers of apoptotic cells in the smooth muscle layer correlated signi®cantly with the expressions of Myc and Bax (r=0.7360 and 0.7432, respectively; both P<0.005), and with the expression index of Bax/Bcl-2 and Bax/Bcl-X L (r=0.8909 and 0.8592, respectively; both P<0.001). Conclusions Apoptosis-related proteins might be important in regulating cell apoptosis in ureteric damage during the development of obstructive uropathy.

Expression of apoptosis-related factors in muscles infected withTrichinella spiralis

“…Reportedly, BAX induces apoptosis by forming the membrane pore in mitochondria from which cytochrome c is released upon apoptotic signalling (Desagher & Martinou, 2000 ;Gottlieb, 2000 ;Tsujimoto & Shimizu, 2000 ;Parone, James & Martinou, 2002). An increase of BAX expression is probably responsible for other types of muscle disorders (Monici et al 1998 ;Lee, Lee & Lee, 2001 ;Chuang et al 2002 ;Ikezoe et al 2002 ;Tews, 2002 ;Umaki et al 2002). Apaf-1 is a co-apoptotic factor and caspase 9 is an initiator caspase, both of which likely play roles in cascades that lead to cell death (Saleh et al 1999 ;Desagher & Martinou, 2000 ;Parone et al 2002).…”

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

“…Ureteric obstruction might lead to severe renal and ureteric injury [1,2]. In our previous studies we established a rat model of obstructive uropathy [2,19,21] and showed that cell apoptosis was related to tissue damage and fibrosis in the smooth muscle layer of obstructed ureters [3,4]. In the present study, the release of cytochrome c and caspase activation were involved in ureteric myocyte apoptosis.…”

“…Apart from renal injuries obstructive uropathy leads to ureteric damage, including hydroureter, hypertrophy and fibrotic changes of ureteric smooth muscle [1,2]. In our previous studies we found that cell apoptosis, and the expression of Fas, TNF-receptor 1 and apoptosis-related proteins were correlated with tissue damage and fibrosis in the smooth muscle layer of obstructed ureters [3,4]. Renal cell apoptosis has been reported in chronic obstructive uropathy, and the activation of caspases suggested to be involved in this process during obstructive uropathy [5].…”

Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in response to partial ureteric obstruction

“…Previously, we used several complete ureteric obstruction animal models to evaluate the effects of ureteric obstruction on renal and ureteric dysfunctions. These studies showed that complete ureteric obstruction resulted in apoptosis-related protein overexpression [ 18 ] . Moreover, we highlighted the fact that cyclooxygenase and/or nuclear factor κ B (NK-κ B) inhibitors could ameliorate ureteric damage [ 19,20 ] .…”

“…In response to increased intra-tubular pressure, tubular cells underwent apoptosis via caspase-dependent pathways. It has been suggested that an inhibition of apoptosis could prevent the subsequent renal infl ammation and fi brosis [ 18,32 ] . During the early stage of interstitial fi brogenesis, there was also an increase in tubular epithelium cell proliferation [ 32 ] .…”