Dataset Information

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.

Conclusion

POC may attenuate I/R injury by reducing mitochondrial oxidative stress and mtDNA damage and sustaining MMP.

SUBMITTER: Tan X

PROVIDER: S-EPMC3811057 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Postconditioning ameliorates mitochondrial DNA damage and deletion after renal ischemic injury.

Tan Xiaohua X Zhang Lei L Jiang Yunpeng Y Yang Yujia Y Zhang Wenqi W Li Yulin Y Zhang Xiuying X

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20130910 11

<h4>Background</h4>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.<h4>Methods</h4>Rats were divided into seven groups: (i) Sham-operated animals with an uncons ...[more]

PMID: 24021677

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Project description:Mitochondrial dysfunction is a predominant risk factor in ischemic heart disease, in which the imbalance of mitochondrial fusion and fission deteriorates mitochondrial function and might lead to cardiomyocyte death. C-phycocyanin (C-pc), an active component from blue-green algae, such as Spirulina platensis, has been reported to have anti-apoptosis and anti-oxidation functions. In this study, the effects of C-pc on mitochondrial dynamics of cardiomyocytes was examined using an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, an in vitro model to study the ischemia in the heart. Cell viability assay showed that C-pc dose-dependently reduced OGD/R-induced cell death. Intracellular reactive oxygen species production induced by OGD/R was decreased in C-pc-treated groups in a dose-dependent manner as well. H9c2 cells subjected to OGD/R showed excessive mitochondrial fission and diminished mitochondrial fusion. C-pc treatment significantly ameliorated unbalanced mitochondrial dynamics induced by OGD/R and regulated mitochondrial remodeling through inhibiting mitochondrial fission while promoting fusion. The enhanced expressions of dynamin 1-like protein and mitochondrial fission 1 protein induced by OGD/R were suppressed by C-pc, while the subdued expressions of mitochondrial fusion proteins mitofusins 1 and 2 and optic atrophy 1 induced by OGD/R increased in C-pc-treated groups. Triple immunofluorescence staining revealed that C-pc treatment reduced the recruitment of dynamin 1-like protein from cytoplasm to mitochondrial membranes. Furthermore, C-pc protected H9c2 cells against OGD/R-induced cytochrome c/apoptotic protease activating factor-1 intrinsic apoptosis and suppressed the phosphorylations of extracellular signal-regulated kinase and c-Jun N-terminal kinase. These results suggest that C-pc protects cardiomyocytes from ischemic damage by affecting mitochondrial fission and fusion dynamics and reducing apoptosis and, thus, may be of potential as a prophylactic or therapeutic agent for ischemic heart disease.

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Dataset Information

Postconditioning ameliorates mitochondrial DNA damage and deletion after renal ischemic injury.

Background

Methods

Results

Conclusion

Publications

Postconditioning ameliorates mitochondrial DNA damage and deletion after renal ischemic injury.

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