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SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity
Liu, Jingxin1; Li, Dan1; Zhang, Tian1; Tong, Qiang2; Ye, Richard Dequan1; Lin, Ligen1
2017-10
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume8
Abstract

Evidences of oxidative stress and mitochondrial dysfunction have been recognized in most of clinical and experimental liver diseases. SIRT3, a member of NAD(+)-dependent deacetylases, is mainly localized in mitochondria. So far, the role of SIRT3 in protecting hepatocytes against oxidative stress remains elusive. Herein, we found SIRT3 protein expression is decreased in tertbutyl hydroperoxide (t-BHP)-treated AML12 cells in vitro and primary hepatocytes from CCI4-injured mice in vivo. To further verify the role of SIRT3 in protecting hepatocytes from t-BHP-induced injury, SIRT3 overexpressed AML12 cell line and primary hepatocytes were generated. SIRT3 overexpressed hepatocytes showed improved cell viability upon t-BHP challenge, with less intracellular reactive oxygen species (ROS) accumulation. SIRT3 overexpression reduced superoxide dismutase 2 acetylation level and stimulated nuclear factor erythroid 2-related factor 2 nuclear translocation to enhance anti-oxidative capacity. Moreover, SIRT3 deacetylated peroxisome proliferator-activated receptor. coactivator 1 alpha to promote mitochondrial biogenesis, and 8-oxoguanine DNA glycosylase 1 to orchestrate DNA repair, resulting in improved mitochondrial function. Through deacetylating Ku70, SIRT3 also abated mitochondrial translocation of dynamin-related protein 1, to attenuate mitochondrial fragmentation in t-BHP-injured hepatocytes. These results suggested that SIRT3 protected hepatocytes against oxidative stress by enhancing ROS scavenging and maintaining mitochondrial integrity.

DOI10.1038/cddis.2017.564
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000414022900001
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
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Cited Times [WOS]:27   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLin, Ligen
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Macau, China
2.Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Liu, Jingxin,Li, Dan,Zhang, Tian,et al. SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity[J]. CELL DEATH & DISEASE,2017,8.
APA Liu, Jingxin,Li, Dan,Zhang, Tian,Tong, Qiang,Ye, Richard Dequan,&Lin, Ligen.(2017).SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity.CELL DEATH & DISEASE,8.
MLA Liu, Jingxin,et al."SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity".CELL DEATH & DISEASE 8(2017).
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