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Protective effects of mitochondrion-targeted peptide SS-31 against hind limb ischemia-reperfusion injury

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Abstract

Hind limb ischemia-reperfusion injury is an important pathology in vascular surgery. Reactive oxygen species are thought to be involved in the pathogenesis of hind limb ischemia-reperfusion injury. SS-31, which belongs to a family of mitochondrion-targeted peptide antioxidants, was shown to reduce mitochondrial reactive oxygen species production. In this study, we investigated whether the treatment of SS-31 could protect hind limb from ischemia-reperfusion injury in a mouse model. The results showed that SS-31 treatment either before or after ischemia exhibited similar protective effects. Histopathologically, SS-31 treatment prevented the IR-induced histological deterioration compared with the corresponding vehicle control. SS-31 treatment diminished oxidative stress revealed by the reduced malondialdehyde level and increased activities and protein levels of Sod and catalase. Cellular ATP contents and mitochondrial membrane potential increased and the level of cytosolic cytC was decreased after SS-31 treatment in this IR model, demonstrating that mitochondria were protected. The IR-induced increase of levels of inflammatory factors, such as Tnf-α and Il-1β, was prevented by SS-31 treatment. In agreement with the reduced cytosolic cytC, cleaved-caspase 3 was kept at a very low level after SS-31 treatment. Overall, the effect of SS-31 treatment before ischemia is mildly more effective than that after ischemia. In conclusion, our results demonstrate that SS-31 confers a protective effect in the mouse model of hind limb ischemia-reperfusion injury preventatively and therapeutically.

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Funding

This work was supported by the National Natural Science Foundation of China (grant number: 81370387).

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Authors and Affiliations

  1. Department of Vascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing, 210008, China

    Jing Cai & Tong Qiao

  2. Department of Vascular Surgery, Drum Tower Hospital, Medical School of Southeast University, Nanjing, 210008, China

    Yu Jiang

  3. Department of Vascular Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, 210008, China

    Meng Zhang

  4. Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, China

    Hongting Zhao, Huihui Li & Kuanyu Li

  5. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China

    Xin Zhang

Authors
  1. Jing Cai
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  2. Yu Jiang
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  3. Meng Zhang
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  4. Hongting Zhao
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  5. Huihui Li
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  6. Kuanyu Li
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  7. Xin Zhang
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  8. Tong Qiao
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Corresponding authors

Correspondence to Xin Zhang or Tong Qiao.

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Experiments were approved by the Animal Investigation Ethic Committee of Nanjing University and were carried out in accordance with the National Institutes of Health (NIH Publication No. 85-23, revised 1996).

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The authors declare that they have no conflict of interest.

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Cai, J., Jiang, Y., Zhang, M. et al. Protective effects of mitochondrion-targeted peptide SS-31 against hind limb ischemia-reperfusion injury. J Physiol Biochem 74, 335–343 (2018). https://doi.org/10.1007/s13105-018-0617-1

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  • DOI: https://doi.org/10.1007/s13105-018-0617-1

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