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http://ntur.lib.ntu.edu.tw/handle/246246/169128
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| Title: | Adenovirus-Mediated Bcl-2 Gene Transfer Inhibits Renal Ischemia/ Reperfusion Induced Tubular Oxidative Stress and Apoptosis |
| Authors: | 鄭劍廷;賴明坤
CHIEN, CHIANG-TING;LAI, MING-KUEN |
| Contributors: | 醫學研究部 |
| Date: | 2005 |
| Issue Date: | 2009-09-30T07:39:35Z |
| Abstract: | Ischemia/reperfusion induces oxidative injury to proximal and distal renal tubular cells. We hypothesize that Bcl-2 protein augmentation with adenovirus vector mediated bcl-2 ( Adv-bcl-2) gene transfer may improve ischemia/reperfusion induced renal proximal and distal tubular apoptosis through the mitochondrial control of Bax and cytochrome C translocation. Twenty-four hours of Adv-bcl-2 transfection to proximal and distal tubular cells in vitro upregulated Bcl-2/Bax ratio and inhibited hypoxia/ reoxygenation induced cytochrome C translocation, O2 production and tubular apoptosis. Intra-renal arterial Adv-bcl-2 administration with renal venous clamping augmented Bcl-2 protein of rat kidney in vivo in a time-dependent manner. The maximal Bcl-2 protein expression appeared at 7 days after Adv-bcl-2 administration and the primary location of Bcl-2 augmentation was in proximal and distal tubules, but not in glomeruli. With a real-time monitoring O2 production and apoptosis analysis of rat kidneys, ischemia/reperfusion increased renal O2 level, potentiated proapoptotic mechanisms, including decrease in Bcl-2/Bax ratio, increases in caspase 3 expression and poly-(ADP-ribose)-polymerase fragments and subsequent proximal and distal tubular apoptosis. However, Adv-bcl-2 administration significantly enhanced Bcl-2/Bax ratio, decreased ischemia/ reperfusion induced O2 amount, inhibited proximal and distal tubular apoptosis and improved renal function. Our results suggest that Adv-bcl-2 gene transfer significantly reduces ischemia/ reperfusion induced oxidative injury in the kidney. |
| Relation: | AMERICAN JOURNAL OF TRANSPLANTATION v.5 n.6 pp.1194-1203 |
| Appears in Collections: | [附設醫院醫學研究部] 期刊論文
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