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Sirt1 Deficiency Upregulates Glutath...

Qiu, Pengxiang.

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Sirt1 Deficiency Upregulates Glutathione Metabolism to Prevent Hepatocellular Carcinoma Initiation in Mice.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Sirt1 Deficiency Upregulates Glutathione Metabolism to Prevent Hepatocellular Carcinoma Initiation in Mice./
作者:	Qiu, Pengxiang.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	161 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
Contained By:	Dissertations Abstracts International83-02B.
標題:	Biomedical engineering. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28548572
ISBN:	9798534654257

Sirt1 Deficiency Upregulates Glutathione Metabolism to Prevent Hepatocellular Carcinoma Initiation in Mice.
Qiu, Pengxiang.

Sirt1 Deficiency Upregulates Glutathione Metabolism to Prevent Hepatocellular Carcinoma Initiation in Mice. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 161 p.

Source: Dissertations Abstracts International, Volume: 83-02, Section: B.

Thesis (Ph.D.)--University of Macau, 2021.

This item must not be sold to any third party vendors.

Sirt1 has been demonstrated to play important role in cancer development. As a master of metabolism regulator, Sirt1 in liver cancer has a dual facet. Liver cancer has been an increasing health killer due to the prevalence of metabolic dysfunction. It is essential to find out Sirt1's function and the potential target for HCC therapy. Here, using Sirt1 liver specific knockout (LKO) mice in combination with diethylnitrosamine (DEN) treatment, we demonstrated that loss of Sirt1 rendered mice to resist hepatocellular carcinoma (HCC) development. Sirt1 null hepatocytes are less damaged by DEN as indicating by phospha-H2AX. RNA-seq data revealed that, the LKO livers exhibited the enrichment in glutathione metabolism 8 months after DEN challenge. Sirt1 deficiency forced Nrf2 translocation to nucleus and elicited the expression of glutathione-s-transferase family so that LKO liver displayed reductive environment with increased ratio of GSH to GSSG. Knockout Nrf2 in LKO liver after DEN increased HCC formation. NAC treatment at 1 month after DEN challenge reversed liver tumor formation in wild type mice, which phenocopied the effects of Sirt1 depletion. However, NAC treatment starting from 5 months after DEN injection was not able to rescue tumor development. Our findings indicate that a reductive environment orchestrated by glutathione metabolism at early stage can prevent initiation of liver cancer.

ISBN: 9798534654257Subjects--Topical Terms:

535387
Biomedical engineering.
Subjects--Index Terms:

Glutathione metabolism

Sirt1 Deficiency Upregulates Glutathione Metabolism to Prevent Hepatocellular Carcinoma Initiation in Mice.
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