title: Postconditioning ameliorates mitochondrial DNA damage and deletion after renal ischemic injury.
abstract: BACKGROUND
  Reactive oxygen species (ROS) play a major role in causing injury in ischemia-reperfusion (I/R). Mitochondrial DNA (mtDNA) is particularly vulnerable to oxidative damage. We propose that increased mitochondrial ROS production is likely to damage mtDNA, causing further injury to mitochondria, and postconditioning (POC) may ameliorate kidney I/R injury by mitigating mitochondrial damage.
  
  
  METHODS
  Rats were divided into seven groups: (i) Sham-operated animals with an unconstricted renal artery; (ii) Sham + 5-hydroxydecanoate (5-HD); (iii) I/R; (iv) I/R + 5-HD; (v) POC; (vi) Sham POC and (vii) POC + 5-HD. Renal injury, oxidative DNA damage, mtDNA deletions, mitochondrial membrane potential (MMP) and expression of the ATP-sensitive K(+) (KATP) channel subunit Kir6.2 were evaluated.
  
  
  RESULTS
  Following 1 h of reperfusion, animals in the I/R group exhibited increased ROS, oxidative mtDNA damage shown by 8-hydroxy-2-deoxyguanosine staining, multiple base pair deletions and decreased MMP. However, POC rats exhibited less ROS, oxidative mtDNA damage and deletions and improved MMP. After 2 days of reperfusion, serum creatinine was elevated in I/R rats and the number of TdT-mediated dUTP nick-end labeled-positive tubular cells was increased and was associated with activation of caspase-3. Therefore, POC prevented the deleterious effects of I/R injury. Furthermore, the expression of mitochondrial Kir6.2 was widely distributed in renal tubular epithelial cells in Sham and POC rats and was lower in I/R rats. All of the protective effects of POC were reversed by the K(+) (KATP) channel blocker 5-HD.
  
  
  CONCLUSIONS
  POC may attenuate I/R injury by reducing mitochondrial oxidative stress and mtDNA damage and sustaining MMP.
authors.affiliation: Department of Pathology, Norman Bethune School of Medicine, Jilin University, Jilin, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yujia
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D007124:Immunoenzyme Techniques; D057775:Ischemic Postconditioning; D007677:Kidney Function Tests; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000099161:Kcnj11 Channel
chemical_list: D053148:Caspase 3; D004272:DNA, Mitochondrial; D024661:Potassium Channels, Inwardly Rectifying; D017382:Reactive Oxygen Species; D000099161:Kcnj11 Channel
keywords: mitochondrial DNA; mitochondrial K+ (KATP) channel; postconditioning; reactive oxygen species; renal protection
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