title: A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation.
abstract: Alcohol dehydrogenase 5 (ADH5) is a conserved enzyme for alcohol and aldehyde metabolism in mammals. Despite dynamic expression throughout neurogenesis, its role in neuronal development remains unknown. Here we present the first evidence that ADH5 is a negative regulator of neuronal differentiation. Gene expression analyses identify a constant reduction of ADH5 levels throughout neuronal development. Overexpression of ADH5 reduces both development and adult neuronal differentiation of mouse neurons. This effect depends on the catalytic activity of ADH5 and involves ADH5-mediated denitrosation of histone deacetylase 2 (HDAC2). Our results indicate that ADH5 counteracts neuronal differentiation of human neural stem cells and that this effect can be reversed by pharmacological inhibition of ADH5. Based on these observations, we propose that ADH5 is a novel suppressor of neuronal differentiation and maturation. Inhibition of ADH5 may improve adult neurogenesis in a physiological or pathological setting.
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Wu
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ruotong
authors.initials: R
authors.lastname: Ren
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Su
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Fei
authors.initials: F
authors.lastname: Yi
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Qiao
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yuan
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: the Department of Microbiology and Immunology, University of California, San Francisco, California, and.
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
authors.affiliation: the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, belmonte@salk.edu.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, the Beijing Institute for Brain Disorders, Beijing 100069, China ghliu@ibp.ac.cn.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Liu
authors.affiliation: From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, the Beijing Institute for Brain Disorders, Beijing 100069, China changchen@moon.ibp.ac.cn.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology / Q000201:enzymology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D012333:RNA, Messenger; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent; C533423:HDAC2 protein, human; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2
keywords: Alcohol Dehydrogenase (ADH); Neural Stem Cell (NSC); Neurodifferentiation; Neurogenesis; S-Nitrosylation