title: Protective effects of humanin on okadaic Acid-induced neurotoxicities in cultured cortical neurons.
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.
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan, 030001, Shanxi, People's Republic of China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Lingmin
authors.initials: L
authors.lastname: Li
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D019319:Okadaic Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000502:physiology; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin; D016875:tau Proteins; D019319:Okadaic Acid; D054648:Protein Phosphatase 2