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4-OI Protects MIN6 Cells from Oxidative Stress Injury by Reducing LDHA-Mediated ROS Generation.


ABSTRACT: Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow to identify molecules that could be utilized to enhance cell survival and function under oxidative stress. Itaconate, a byproduct of the tricarboxylic acid cycle, has both anti-inflammatory and antioxidant properties. The effects of itaconate on beta cells under oxidative stress are relatively unknown. We explored the effects of 4-octyl itaconate-a cell-permeable derivative of itaconate-on MIN6 (a beta cell model) under oxidative stress conditions caused by hypoxia, along with its mechanism of action. Treatment with 4-OI reversed hypoxia-induced cell death, reduced ROS production, and inhibited cell death pathway activation and inflammatory cytokine secretion in MIN6 cells. The 4-OI treatment also suppressed lactate dehydrogenase A (LDHA)activity, which increases under hypoxia. Treatment of cells with the ROS scavenger NAC and LDHA-specific inhibitor FX-11 reproduced the beneficial effects of 4-OI on MIN6 cell viability under oxidative stress conditions, confirming its role in regulating ROS production. Conversely, overexpression of LDHA reduced the beneficial effects exerted by 4-OI on cells. Our findings provide a strong rationale for using 4-OI to prevent the death of MIN6 cells under oxidative stress.

SUBMITTER: Wu J 

PROVIDER: S-EPMC9496514 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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4-OI Protects MIN6 Cells from Oxidative Stress Injury by Reducing <i>LDHA</i>-Mediated ROS Generation.

Wu Jianmin J   Gu Xingshi X   Zhang Juan J   Mi Ze Z   He Zhenhu Z   Dong Yuqian Y   Ge Wu W   Ghimire Kedar K   Rong Pengfei P   Wang Wei W   Ma Xiaoqian X  

Biomolecules 20220904 9


Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow to identify molecules that could be utilized to enhance cell survival and function under oxidative stress. Itaconate, a byproduct of the tricarboxylic acid cycle, has both anti-inflammatory and antioxidant properties. The effects of itaconate on beta cells under oxidative stress are relatively unknown. We explored the effects of 4-octyl itaconate-a cell-permea  ...[more]

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