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http://ntur.lib.ntu.edu.tw/handle/246246/169129
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| Title: | Bcl-Xl Augmentation Potentially Reduces Ischemia/Reperfusion Induced Proximal and Distal Tubular Apoptosis and Autophagy |
| Authors: | 鄭劍廷;賴明坤
CHIEN, CHIANG-TING;LAI, MING-KUEN |
| Contributors: | 醫學研究部 |
| Date: | 2007 |
| Issue Date: | 2009-09-30T07:40:05Z |
| Abstract: | Background. Apoptosis and autophagy may contribute to cell homeostasis in the kidney subjected to ischemia/reperfusion injury via mitochondrial injury. Ischemia/reperfusion induces differential sensitivity between proximal and distal tubules via a dissociated Bcl-xL expression. We hypothesized Bcl-xL augmentation in the proximal and distal tubules may potentially reduce ischemia/reperfusion induced renal dysfunction. Methods . We augmented Bcl-xL protein expression in the kidney with intrarenal adenoviral bcl-xL gene transfer and evaluated the potential effect of Bcl- xL augmentation on ischemia/reperfusion induced renal oxidative stress, apoptosis, and autophagy in the rat. Results. Intrarenal arterial Adv-bcl- xL administration augmented maximal Bcl-xL protein expression of rat kidney after 7 days of transfection. The primary location of Bcl-xL augmentation was found in proximal and distal tubules, but not in glomeruli. Ischemia/reperfusion increased mitochondrial cytochrome C release, renal O-2(-) level and renal 3-nitrosine and 4-hydroxyneonal accumulation, potentiated tubular apoptosis and autophagy, including increase in microtubule-associated protein 1 light chain 3 ( LC-3) and Beclin-1 expression, Bax/Bcl-xL ratio, caspase 3 expression and poly-(ADP- ribose)-polymerase fragments, and subsequent proximal and distal tubular apoptosis/autophagy. However, Adv-bcl-xL administration significantly reduced ischemia/reperfusion enhanced mitochondrial cytochrome C release, O-2(-) production, 3-nitrotyrosine and 4- hydroxynonenal accumulation, Beclin-1 expression, Bax/Bcl-YL ratio, and proximal and distal tubular apoptosis/autophagy, consequently improving renal dysfunction. Further study showed that Bcl-xL augmentation was more efficiently than Bcl-2 augmentation in amelioration of ischemia/reperfusion induced proximal and distal tubular apoptosis and renal dysfunction. Conclusions. Our results suggest that Adv-bcl- xL gene transfer significantly improves ischemia/ reperfusion -induced renal dysfunction via the downregulation of renal tubular apoptosis and autophagy. |
| Relation: | TRANSPLANTATION v.84 n.9 pp.1183-1190 |
| Appears in Collections: | [附設醫院醫學研究部] Periodical Articles
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