SIRT3 plays a key role in regulation of hepatocytes oxidative stress, Jingxin Liu

UM > Institute of Chinese Medical Sciences

Status	已發表Published
	SIRT3 plays a key role in regulation of hepatocytes oxidative stress, Jingxin Liu
	Liu, J.; Li, D.; Chen, K.; Tong, Q.; Lin, L.
	2016-09-18
Source Publication	Cold Spring Harbor-Asia Conference: Metabolism and Cancer
Abstract	ROS is the main factor contributing to hepatic dysfunction, which is linked to pathology of fibrosis, cirrhosis and even hepatoma. It has been shown SIRT3, the major mitochondrial protein deacetylase, regulates ROS in many organs. However, the extent to which SIRT3 protects hepatocytes from oxidative stress remains elusive. We firstly generated acute and chronic CCl4-induced liver injury mice models and found SIRT3 expression level in liver was decreased in acute model, but unchanged in chronic model. Next we established a SIRT3 overexpressed murine hepatocyte AML12 cell line. SIRT3 overexpression protected AML12 cells from t-BHP induced oxidative injury through reducing ROS accumulation. Further studies revealed SIRT3 overexpression reduced SOD2 acetylation level to increase its activity, resulting in enhanced anti-oxidant capacity. Treatment of t-BHP caused mitochondrial membrane potential reduction and mitochondrial fragmentation, which resulted in mitochondrial dysfunction. Interestingly, SIRT3 overexpression totally reversed these adverse effects through upregulating PGC-1α level to promote mitochondria biogenesis, and promoting NRF2 nuclear translocation to maintain mitochondrial dynamics. Furthermore, t-BHP treatment resulted in nuclear DNA damage, while SIRT3 overexpression repaired DNA through upregulation of OGG1/2 and decreasing its acetylation level. As regard to hepatocyte renewal, SIRT3 overexpression significantly promoted hepatocyte proliferation under oxidative stress. Lastly, we found honokiol, an SIRT3 activator, had ability in reversing acute CCl4-induced hepatic damage. In summary, these results suggest that SIRT3 increases anti-oxidant capacity, maintains mitochondrial homeostasis and improves nuclear DNA repair under oxidative stress status, to enhance hepatocytes surviving, which could be a potential therapy target for liver diseases.
Keyword	SIRT3 liver oxidative stress PGC-1a
Language	英語English
The Source to Article	PB_Publication
PUB ID	29016
Document Type	Conference paper
Collection	Institute of Chinese Medical Sciences
Corresponding Author	Lin, L.
Recommended Citation GB/T 7714	Liu, J.,Li, D.,Chen, K.,et al. SIRT3 plays a key role in regulation of hepatocytes oxidative stress, Jingxin Liu[C], 2016.
APA	Liu, J.., Li, D.., Chen, K.., Tong, Q.., & Lin, L. (2016). SIRT3 plays a key role in regulation of hepatocytes oxidative stress, Jingxin Liu. Cold Spring Harbor-Asia Conference: Metabolism and Cancer.

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