title: Humanin protects cortical neurons from ischemia and reperfusion injury by the increased activity of superoxide dismutase.
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.
authors.affiliation: Department of Physiology, Guangzhou Medical School, Guangzhou 510182, People's Republic of China.
authors.forename: Shen-Ting
authors.initials: ST
authors.lastname: Zhao
authors.forename: Xiao-Tian
authors.initials: XT
authors.lastname: Huang
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
mesh_terms: D002540:Cerebral Cortex / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase