Protective effects of mitochondrion-targeted peptide SS-31 against hind limb ischemia-reperfusion injury
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.
KeywordsSS-31 Hind limb ischemia-reperfusion injury Reactive oxygen species Mitochondria Inflammation
This work was supported by the National Natural Science Foundation of China (grant number: 81370387).
Compliance with ethical standards
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).
Conflict of interest
The authors declare that they have no conflict of interest.
- 8.Comu FM, Kilic Y, Ozer A, Kirisci M, Dursun AD, Tatar T, Zor MH, Kartal H, Kucuk A, Boyunaga H et al (2016) Effect of picroside II on erythrocyte deformability and lipid peroxidation in rats subjected to hind limb ischemia reperfusion injury. Drug Des Dev Ther 10:927–931Google Scholar
- 15.Gokce EC, Kahveci R, Gokce A, Sargon MF, Kisa U, Aksoy N, Cemil B, Erdogan B (2016) Curcumin attenuates inflammation, oxidative stress, and ultrastructural damage induced by spinal cord ischemia-reperfusion injury in rats. J Stroke Cerebrovasc Dis : Off J Natl Stroke Assoc 25:1196–1207CrossRefGoogle Scholar
- 16.Hao S, Ji J, Zhao H, Shang L, Wu J, Li H, Qiao T, Li K (2015) Mitochondrion-targeted peptide SS-31 inhibited oxidized low-density lipoproteins-induced foam cell formation through both ROS scavenging and inhibition of cholesterol influx in RAW264.7 cells. Molecules 20:21287–21297CrossRefPubMedGoogle Scholar
- 28.Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ (2013) Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell 12:763–771CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Takhtfooladi HA, Hesaraki S, Razmara F, Takhtfooladi MA, Hajizadeh H (2016) Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia/reperfusion injury. Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia 42:9–14CrossRefGoogle Scholar
- 45.Zhao WY, Han S, Zhang L, Zhu YH, Wang LM, Zeng L (2013) Mitochondria-targeted antioxidant peptide SS31 prevents hypoxia/reoxygenation-induced apoptosis by down-regulating p66Shc in renal tubular epithelial cells. Cell Physiol Biochem : Int J Exp Cell Physiol Biochem Pharmacol 32:591–600CrossRefGoogle Scholar