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J Biol Chem. 2014 Jul 18;289(29):20193-9. doi: 10.1074/jbc.C114.561860. Epub 2014 Jun 3.

A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation.

Author information

1
From the National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
2
the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
3
the Department of Microbiology and Immunology, University of California, San Francisco, California, and.
4
the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, belmonte@salk.edu.
5
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.
6
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.

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.

KEYWORDS:

Alcohol Dehydrogenase (ADH); Neural Stem Cell (NSC); Neurodifferentiation; Neurogenesis; S-Nitrosylation

PMID:
24895131
PMCID:
PMC4106335
DOI:
10.1074/jbc.C114.561860
[Indexed for MEDLINE]
Free PMC Article

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