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Adenovirus‐Mediated bcl‐2 Gene Transfer Inhibits Renal Ischemia/Reperfusion Induced Tubular Oxidative Stress and Apoptosis
Author(s) -
ChiangTing Chien,
TzuChing Chang,
ChingYi Tsai,
SongKuen Shyue,
MingKuen Lai
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00826.x
Subject(s) - renal ischemia , apoptosis , cytochrome c , medicine , kidney , ischemia , oxidative stress , transfection , reperfusion injury , endocrinology , microbiology and biotechnology , biology , biochemistry , gene
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, O 2 − 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 O 2 − production and apoptosis analysis of rat kidneys, ischemia/reperfusion increased renal O 2 − 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 O 2 − 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.