Article

Humanin protects cortical neurons from ischemia and reperfusion injury by the increased activity of superoxide dismutase.

Department of Physiology, Guangzhou Medical School, Guangzhou 510182, People's Republic of China.
Neurochemical Research (Impact Factor: 2.55). 09/2011; 37(1):153-60. DOI: 10.1007/s11064-011-0593-0
Source: PubMed

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.

0 Bookmarks
 · 
151 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD), which are mostly composed of hyperphosphorylated tau and directly correlate with dementia in AD patients. Okadaic acid (OA), a toxin extracted from marine life, can specifically inhibit protein phosphatases (PPs), including PP1 and Protein phosphatase 2A (PP2A), resulting in tau hyperphosphorylation. Humanin (HN), a peptide of 24 amino acids, was initially reported to protect neurons from AD-related cell toxicities. The present study was designed to test if HN could attenuate OA-induced neurotoxicities, including neural insults, apoptosis, autophagy, and tau hyperphosphorylation. We found that administration of OA for 24 h induced neuronal insults, including lactate dehydrogenase released, decreased of cell viability and numbers of living cells, neuronal apoptosis, cells autophagy and tau protein hyperphosphorylation. Pretreatment of cells with HN produced significant protective effects against OA-induced neural insults, apoptosis, autophagy and tau hyperphosphorylation. We also found that OA treatment inhibited PP2A activity and HN pretreatment significantly attenuated the inhibitory effects of OA. This study demonstrated for the first time that HN protected cortical neurons against OA-induced neurotoxicities, including neuronal insults, apoptosis, autophagy, and tau hyperphosphorylation. The mechanisms underlying the protections of HN may involve restoration of PP2A activity.
    Neurochemical Research 08/2014; · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Humanin is a 24-amino acid, secreted bioactive peptide that prevents various types of cell death and improves some types of cell dysfunction. Humanin inhibits neuronal cell death that is caused by a familial Alzheimer's disease (AD)-linked gene via binding to the heterotrimeric Humanin receptor (htHNR). This suggests that Humanin may play a protective role in AD-related pathogenesis. Calmodulin-like skin protein (CLSP) has recently been identified as a physiological agonist of htHNR with 10(5)-fold more potent anti-cell death activity than Humanin. Humanin has also shown to have protective effects against some metabolic disorders. In this review, the broad range of functions of Humanin and the functions of CLSP that have been characterized thus far are summarized.
    Molecular neurobiology. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Humanin is a potential therapeutic agent for Alzheimer's disease, and its derivative, S14G-humanin, is 1 000-fold stronger in its neuroprotective effect against Alzheimer's disease-relevant insults. Al-though effective, the detailed molecular mechanism through which S14G-humanin exerts its effects remains unclear. Data from this study showed that fibrillar amyloid-beta 40 disturbed cellular ho-meostasis through the cell membrane, increasing intracellular calcium, generating reactive oxygen species, and decreasing the mitochondrial membrane potential. S14G-humanin restored these responses. The results suggested that S14G-humanin blocked the effects of amyloid-beta 40 on the neuronal cell membrane, and restored the disturbed cellular homeostasis, thereby exerting a neu-roprotective effect on hippocampal neurons.
    Neural Regeneration Research 09/2013; 8(27):2573-80. · 0.23 Impact Factor