title: Peroxisome proliferator-activated receptor γ is inhibited by histone deacetylase 4 in cortical neurons under oxidative stress.
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.
authors: Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
authors: Yang
authors: Y
authors: Yang
authors: Xiaocui
authors: X
authors: Qin
authors: Shuhu
authors: S
authors: Liu
authors: Jianjun
authors: J
authors: Li
authors: Xinhong
authors: X
authors: Zhu
authors: Tianming
authors: T
authors: Gao
authors: Xuemin
authors: X
authors: Wang