The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver

Ying Zhang; Jiyoung Park; Seong Jeong Han; Iha Park; Thang Nguyen Huu; Jong Suk Kim; Hyun Ae Woo; Seung Rock Lee

doi:10.1016/j.freeradbiomed.2020.11.022

The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver

Ying Zhang, Jiyoung Park, Seong Jeong Han, Iha Park, Thang Nguyen Huu, Jong Suk Kim, Hyun Ae Woo, Seung Rock Lee

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Hepatic steatosis and subsequent fatty liver disease are developed in response to alcohol consumption. Reactive oxygen species (ROS) are thought to play an important role in the alcoholic fatty liver disease (AFLD). However, the molecular targets of ROS and the underlying cellular mechanisms are unknown. Here, we investigate roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in the alcoholic fatty liver. Alcohol-induced mitochondrial oxidative stress was found to contribute to reversible oxidation of PTEN, which results in Akt and MAPK hyperactivation with elevated levels of the lipogenesis regulators SREBP1c and PPARγ. Moreover, mitochondrial peroxiredoxin III was found to have antagonistic effects on lipogenesis via the redox regulation of PTEN by removing ROS, upon alcohol exposure. This study demonstrated that redox regulation of PTEN and peroxiredoxin III play crucial roles in the development of AFLD.

Original language	English
Pages (from-to)	141-148
Number of pages	8
Journal	Free Radical Biology and Medicine
Volume	162
DOIs	https://doi.org/10.1016/j.freeradbiomed.2020.11.022
State	Published - Jan 2021

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea ( 2018R1D1A1B06051438 , 2015R1D1A1A01059571 , and 2019RIA6C1010020 ), Republic of Korea. Jiyoung Park was supported by the Health Fellowship Foundation.

Publisher Copyright:
© 2020

Keywords

Alcohol
Alcoholic fatty liver disease
Hepatic steatosis
Peroxiredoxin III
PTEN
Reactive oxygen species

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10.1016/j.freeradbiomed.2020.11.022

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title = "The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver",

abstract = "Hepatic steatosis and subsequent fatty liver disease are developed in response to alcohol consumption. Reactive oxygen species (ROS) are thought to play an important role in the alcoholic fatty liver disease (AFLD). However, the molecular targets of ROS and the underlying cellular mechanisms are unknown. Here, we investigate roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in the alcoholic fatty liver. Alcohol-induced mitochondrial oxidative stress was found to contribute to reversible oxidation of PTEN, which results in Akt and MAPK hyperactivation with elevated levels of the lipogenesis regulators SREBP1c and PPARγ. Moreover, mitochondrial peroxiredoxin III was found to have antagonistic effects on lipogenesis via the redox regulation of PTEN by removing ROS, upon alcohol exposure. This study demonstrated that redox regulation of PTEN and peroxiredoxin III play crucial roles in the development of AFLD.",

keywords = "Alcohol, Alcoholic fatty liver disease, Hepatic steatosis, Peroxiredoxin III, PTEN, Reactive oxygen species",

author = "Ying Zhang and Jiyoung Park and Han, {Seong Jeong} and Iha Park and Huu, {Thang Nguyen} and Kim, {Jong Suk} and Woo, {Hyun Ae} and Lee, {Seung Rock}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea ( 2018R1D1A1B06051438 , 2015R1D1A1A01059571 , and 2019RIA6C1010020 ), Republic of Korea. Jiyoung Park was supported by the Health Fellowship Foundation. Publisher Copyright: {\textcopyright} 2020",

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AU - Zhang, Ying

AU - Park, Jiyoung

AU - Han, Seong Jeong

AU - Park, Iha

AU - Huu, Thang Nguyen

AU - Kim, Jong Suk

AU - Woo, Hyun Ae

AU - Lee, Seung Rock

N1 - Funding Information: This work was supported by the National Research Foundation of Korea ( 2018R1D1A1B06051438 , 2015R1D1A1A01059571 , and 2019RIA6C1010020 ), Republic of Korea. Jiyoung Park was supported by the Health Fellowship Foundation. Publisher Copyright: © 2020

PY - 2021/1

Y1 - 2021/1

N2 - Hepatic steatosis and subsequent fatty liver disease are developed in response to alcohol consumption. Reactive oxygen species (ROS) are thought to play an important role in the alcoholic fatty liver disease (AFLD). However, the molecular targets of ROS and the underlying cellular mechanisms are unknown. Here, we investigate roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in the alcoholic fatty liver. Alcohol-induced mitochondrial oxidative stress was found to contribute to reversible oxidation of PTEN, which results in Akt and MAPK hyperactivation with elevated levels of the lipogenesis regulators SREBP1c and PPARγ. Moreover, mitochondrial peroxiredoxin III was found to have antagonistic effects on lipogenesis via the redox regulation of PTEN by removing ROS, upon alcohol exposure. This study demonstrated that redox regulation of PTEN and peroxiredoxin III play crucial roles in the development of AFLD.

AB - Hepatic steatosis and subsequent fatty liver disease are developed in response to alcohol consumption. Reactive oxygen species (ROS) are thought to play an important role in the alcoholic fatty liver disease (AFLD). However, the molecular targets of ROS and the underlying cellular mechanisms are unknown. Here, we investigate roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in the alcoholic fatty liver. Alcohol-induced mitochondrial oxidative stress was found to contribute to reversible oxidation of PTEN, which results in Akt and MAPK hyperactivation with elevated levels of the lipogenesis regulators SREBP1c and PPARγ. Moreover, mitochondrial peroxiredoxin III was found to have antagonistic effects on lipogenesis via the redox regulation of PTEN by removing ROS, upon alcohol exposure. This study demonstrated that redox regulation of PTEN and peroxiredoxin III play crucial roles in the development of AFLD.

KW - Alcohol

KW - Alcoholic fatty liver disease

KW - Hepatic steatosis

KW - Peroxiredoxin III

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KW - Reactive oxygen species

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ER -

The critical role of redox regulation of PTEN and peroxiredoxin III in alcoholic fatty liver

Abstract

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