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Humanin Protects Cortical Neurons from Ischemia and Reperfusion Injury by the Increased Activity of Superoxide Dismutase

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Abstract

The neuroprotective effects of superoxide dismutase (SOD) against hypoxia/reperfusion (I/R) injury and of humanin (HN) against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant SOD led us to hypothesize that HN might have a role to increase the activity of SOD, which might be involved in the protective effects of HN on neuron against Alzheimer’s disease-unrelated neurotoxicities. In the present study, we found that 4 h ischemia and 24 h reperfusion induced a significant increase in lactate dehydrogenase (LDH) release, malondialdehyde (MDA) formation and the number of karyopyknotic nuclei (4′,6-diamidino-2-phenylindole dihydrochloride nuclear dyeing) and a decrease in the number of Calcein-AM-positive living cells and cell viability. Pretreatment of the cells with HN led to a significant decrease in LDH release, MDA formation and the number of karyopyknotic nuclei, and an increase in the number of Calcein-AM-positive living cells and cell viability in neurons treated with I/R. We also found a significant decrease in SOD activity in neurons treated with I/R only, while pre-treatment with HN before I/R induced a significant increase in the activity of SOD as compared with the I/R group. Our findings implied that HN protects cortical neurons from I/R injury by the increased SOD activity and that the protective effect of HN on neurons against I/R is concentration-dependent.

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Acknowledgments

The studies in our laboratories were supported by research grants from Guangzhou Medical School, The Chinese University of Hong Kong, and Shanxi Medical University, the Competitive Earmarked Grants of Hong RGC (CUHK466907-KY), and NSFC-RGC Joint Research Grant (N-CUHK433/08). We declare that we have no financial interests.

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Authors and Affiliations

  1. Department of Physiology, Guangzhou Medical School, Guangzhou, 510182, People’s Republic of China

    Shen-Ting Zhao

  2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

    Shen-Ting Zhao, Xiao-tian Huang & Ya Ke

  3. Department of Neurobiology, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China

    Ce Zhang

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  1. Shen-Ting Zhao
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Correspondence to Ya Ke.

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Zhao, ST., Huang, Xt., Zhang, C. et al. Humanin Protects Cortical Neurons from Ischemia and Reperfusion Injury by the Increased Activity of Superoxide Dismutase. Neurochem Res 37, 153–160 (2012). https://doi.org/10.1007/s11064-011-0593-0

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  • DOI: https://doi.org/10.1007/s11064-011-0593-0

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