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Peroxisome proliferator‐activated receptor γ is inhibited by histone deacetylase 4 in cortical neurons under oxidative stress
Author(s) -
Yang Yang,
Qin Xiaocui,
Liu Shuhu,
Li Jianjun,
Zhu Xinhong,
Gao Tianming,
Wang Xuemin
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07316.x
Subject(s) - hdac4 , peroxisome proliferator activated receptor , microbiology and biotechnology , histone deacetylase , gene knockdown , oxidative stress , transcription factor , receptor , biology , psychological repression , nuclear receptor , hdac1 , histone , chemistry , gene expression , biochemistry , gene
J. Neurochem. (2011) 118 , 429–439. Abstract Peroxisome proliferator‐activated receptor γ (PPARγ) serves an essential protective function in neurons. Although PPARγ activation is known to reduce brain tissue damage in distinct models of brain diseases, the regulation of PPARγ activity in neurons is unclear. Here, we report that histone deacetylase 4 (HDAC4) mediates PPARγ inhibition in cultured cortical neurons under oxidative stress. Our data indicate that HDAC4 physically interacts with PPARγ and represses PPARγ transcription activity in cultured cortical neurons. Upon H 2 O 2 treatment, HDAC4 translocates from the cytoplasm to the nucleus, where it inhibits PPARγ transcription. This inhibition rendered neurons more vulnerable to H 2 O 2 insult. In contrast, knockdown of HDAC4 by introduction of a specific microRNA abolishes the oxidative stress‐induced repression of PPARγ in neurons and also reduces the number of dead neurons induced by H 2 O 2. Furthermore, over‐expression of PPARγ protects neurons from either HDAC4 over‐expression‐ or H 2 O 2 ‐induced damage. These data suggest that HDAC4 works to repress PPARγ transcription and regulates neuronal death by inhibiting PPARγ pro‐survival activity.