Humanin Rescues Cortical Neurons From Hypoxia-induced Insults

Alzheimer's disease(AD) is the neurodegenerative disease characterized by senile plaque, neurofibrillary tangles, progressive neuronal loss. Despite the progressive nature of neurodegeneration, the occipital lobe in AD brains is rarely affected by the disease. This phenomenon arouse the interesting of researchers and finally led to the newly discovered a 24-aa polypeptide named Humanin (HN). Studies showed that HN can inhibit full length Aβpeptide and Aβ25-35 fragment induced neuronal death. In addition, evidence showed that HN also suppressed family gene mutation induced neuronal injury such as PS1, PS2. Thus, HN was defined to be a neuroprotective peptide specially against AD related insults. Subsequently efforts toward understanding the mechanisms underlying HN against AD related insults have been employed, and several mechanisms were involved in the neuroprotection of HN, although it is not entirely understood, including depressing Ca2+ overloading to maintain Ca2+ homeostasis; increasing ATP levels to improve cellular function; inhibiting mitochondrial pathway apoptosis by preventing the translocation of Bax from cytosol to mitochondria; inhibiting death receptor pathway apoptosis by suppressing JNK-c-jun mediated expression of FasL. Consideration of neuroprotective mechanism of HN reported so far strongly suggested that HN might be a broader protective factor for variouse neurotoxicity rather than just for AD related insults. Some reports supported this viewpoint , Shingo Kariya et al. reported that HN could depress scopolamine-induced impairment and serum-deprivation-induced cell death of PC12h cells. To explore this hypothesis for broader protection of HN, we designed this experiment to investigate whether HN has protective effects on neuronal insults induced by hypoxia or hypoxia plus reperfusion.There are two parts of experiment. In the first part, three kinds of substances related hypoxia injury were measured: malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH). MDA is originated from membrane lipid attacked by oxygen free radicals, so the level of lipid peroxidation were determined by analyzing MDA production; SOD is a kind...