Upregulation of Znf179 acetylation by SAHA protects cells against oxidative stress
Chung-Che Wu,
Pin-Tse Lee,
Tzu-Jen Kao,
Szu-Yi Chou,
Ruei-Yuan Su,
Yi-Chao Lee,
Shiu-Hwa Yeh,
Jing-Ping Liou,
Tsung-I Hsu,
Tsung-Ping Su,
Cheng-Keng Chuang,
Wen-Chang Chang,
Jian-Ying Chuang
Affiliations
Chung-Che Wu
Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taiwan; Division of Neurosurgery, Department of Surgery, Taipei Medical University Hospital, Taiwan
Pin-Tse Lee
Cellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, USA
Tzu-Jen Kao
The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan
Szu-Yi Chou
The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan
Ruei-Yuan Su
Graduate Institute of Medical Science, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan
Yi-Chao Lee
The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan
Shiu-Hwa Yeh
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan
Jing-Ping Liou
School of Pharmacy, Taipei Medical University, Taiwan
Tsung-I Hsu
Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taiwan
Tsung-Ping Su
Cellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, USA
Cheng-Keng Chuang
Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taiwan
Wen-Chang Chang
Graduate Institute of Medical Science, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan; Corresponding author.
Jian-Ying Chuang
The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan; School of Pharmacy, Taipei Medical University, Taiwan; Corresponding author at: The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
The accumulation of reactive oxygen species (ROS) commonly occurs during normal aging and during some acute/chronic progressive disorders. In order to avoid oxidative damage, scavenging of these radicals is important. Previously, we identified zinc finger protein 179 (Znf179) as a neuroprotector that increases antioxidant enzymes against superoxide radicals. However, the molecular mechanisms involved in the activation and regulation of Znf179 remain unresolved. Here, by performing sequence alignment, bioinformatics analysis, immunoprecipitation using two specific acetyl-lysine antibodies, and treatment with the histone deacetylase (HDAC) inhibitor SAHA, we determined the lysine-specific acetylation of Znf179. Furthermore, we investigated Znf179 interaction with HDACs and revealed that peroxide insult induced a dissociation of Znf179-HDAC1/HDAC6, causing an increase in Znf179 acetylation. Importantly, HDAC inhibition by SAHA further prompted Znf179 hyperacetylation, which promoted Znf179 to form a transcriptional complex with Sp1 and increased antioxidant gene expression against oxidative attack. In summary, the results obtained in this study showed that Znf179 was regulated by HDACs and that Znf179 acetylation was a critical mechanism in the induction of antioxidant defense systems. Additionally, HDAC inhibitors may have therapeutic potential for induction of Znf179 acetylation, strengthening the Znf179 protective functions against neurodegenerative processes. Keywords: Znf179, SAHA, HDACs, Oxidative stress, Antioxidants
