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

Chiang Ting Chien, Tzu Ching Chang, Ching Yi Tsai, Song Kuen Shyue, Ming Kuen Lai

Research output: Contribution to journalArticle

89 Citations (Scopus)

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 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 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.

Original languageEnglish
Pages (from-to)1194-1203
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number6
DOIs
Publication statusPublished - 2005 Jun

Keywords

  • Apoptosis
  • Bcl-2
  • Gene transfer
  • Ischemia/reperfusion
  • Kidney
  • Oxidative stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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