title: Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain.
abstract: Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca(2+)]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome.
authors.affiliation: 1] Department of Biology, College of Natural Sciences (RINS) and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea [2] Center of Excellence in Genomic Medicine and Research (CEGMR) King Abdulaziz University, PO Box 80216, Jeddah 21589, Saudi Arabia.
authors.forename: M I
authors.initials: MI
authors.lastname: Naseer
authors.affiliation: Department of Biology, College of Natural Sciences (RINS) and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: I
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907-2010, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Narasimhan
authors.affiliation: Department of Biology, College of Natural Sciences (RINS) and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: H Y
authors.initials: HY
authors.lastname: Lee
authors.affiliation: 1] Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907-2010, USA [2] Department of Biochemistry and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: R A
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Department of Biology, College of Natural Sciences (RINS) and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: G H
authors.initials: GH
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: D J
authors.initials: DJ
authors.lastname: Yun
authors.affiliation: Department of Biology, College of Natural Sciences (RINS) and Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: M O
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology*; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010940:Plant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D010940:Plant Proteins; D054419:Receptors, Adiponectin; C073139:osmotin protein, Nicotiana tabacum; D000431:Ethanol; D000263:Adenylate Kinase