Adenovirus-mediated bcl-2 gene transfer inhibits renal ischemia/reperfusion induced tubular oxidative stress and apoptosis

Am J Transplant. 2005 Jun;5(6):1194-203. doi: 10.1111/j.1600-6143.2005.00826.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Apoptosis
  • Caspases / metabolism
  • Cytochromes c / metabolism
  • Female
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Kidney Tubules, Distal / drug effects*
  • Kidney Tubules, Distal / metabolism
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism
  • Oxidative Stress
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*


  • Proto-Oncogene Proteins c-bcl-2
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Caspases