摘要

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.
原文英語
頁(從 - 到)74-80
頁數7
期刊Redox Biology
19
DOIs
出版狀態已發佈 - 十月 1 2018

指紋

Acetylation
Oxidative stress
Zinc Fingers
Zinc
Oxidative Stress
Up-Regulation
Proteins
Histone Deacetylase Inhibitors
Antioxidants
Lysine
Histone Deacetylases
Sequence Alignment
Scavenging
Peroxides
Bioinformatics
Computational Biology
Immunoprecipitation
Gene expression
Superoxides
Reactive Oxygen Species

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

引用此文

Upregulation of Znf179 acetylation by SAHA protects cells against oxidative stress. / Wu, Chung Che; Lee, Pin Tse; Kao, Tzu Jen; Chou, Szu Yi; Su, Ruei Yuan; Lee, Yi Chao; Yeh, Shiu Hwa; Liou, Jing Ping; Hsu, Tsung I.; Su, Tsung Ping; Chuang, Cheng Keng; Chang, Wen Chang; Chuang, Jian Ying.

於: Redox Biology, 卷 19, 01.10.2018, p. 74-80.

研究成果: 雜誌貢獻文章

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title = "Upregulation of Znf179 acetylation by SAHA protects cells against oxidative stress",
abstract = "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.",
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author = "Wu, {Chung Che} and Lee, {Pin Tse} and Kao, {Tzu Jen} and Chou, {Szu Yi} and Su, {Ruei Yuan} and Lee, {Yi Chao} and Yeh, {Shiu Hwa} and Liou, {Jing Ping} and Hsu, {Tsung I.} and Su, {Tsung Ping} and Chuang, {Cheng Keng} and Chang, {Wen Chang} and Chuang, {Jian Ying}",
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T1 - Upregulation of Znf179 acetylation by SAHA protects cells against oxidative stress

AU - Wu, Chung Che

AU - Lee, Pin Tse

AU - Kao, Tzu Jen

AU - Chou, Szu Yi

AU - Su, Ruei Yuan

AU - Lee, Yi Chao

AU - Yeh, Shiu Hwa

AU - Liou, Jing Ping

AU - Hsu, Tsung I.

AU - Su, Tsung Ping

AU - Chuang, Cheng Keng

AU - Chang, Wen Chang

AU - Chuang, Jian Ying

N1 - Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - Antioxidants

KW - HDACs

KW - Oxidative stress

KW - SAHA

KW - Znf179

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