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  • Title: Mitochondria-targeted antioxidant peptide SS31 prevents hypoxia/reoxygenation-induced apoptosis by down-regulating p66Shc in renal tubular epithelial cells.
    Author: Zhao WY, Han S, Zhang L, Zhu YH, Wang LM, Zeng L.
    Journal: Cell Physiol Biochem; 2013; 32(3):591-600. PubMed ID: 24021885.
    Abstract:
    BACKGROUND/AIMS: Ischemia/reperfusion injury plays a crucial role in renal transplantation and represents a significant risk factor for acute kidney injury and delayed graft function. Mitochondria-targeted antioxidant peptide SS31 has been shown to attenuate ischemia/reperfusion injury by inhibiting oxidative stress. The present study was carried out to investigate whether the pretreatment of SS31 could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting p66Shc. METHODS: The cultured rat renal proximal tubular cell line NRK52E cells were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 6 h reoxygenation (5% CO2, 21% O2, 74% N2). SS31 was added to the culture medium 4 h prior to the treatment. Then the cell viability, apoptosis, and oxidative stress levels were determined. In addition, western blot analysis was performed to determine the expression of p66Shc, p-p66Shc, cytochrome c, and caspase-3. RESULTS: H/R induced apoptotic cell death, accompanied with activation of total and p-p66Shc in NRK52E cells. Pretreatment with SS31 or overexpression of a dominantnegative Ser36 mutant p66Shc (p66Shc S36A) or p66Shc siRNA prevented cell death, whereas the protection effect of SS31 was completely blocked by overexpression of wild-type p66Shc. Furthermore, SS31 pretreatment reduced H/R-induced intracellular oxidative stress, cytochrome c translocation to the cytoplasm, and caspase-3 activation through inhibiting p66Shc. CONCLUSION: This study revealed that SS31 pretreatment serves a protective role against H/R-induced apoptosis of human renal tubular epithelial cells, and the mechanism is related to suppression of p66Shc.
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