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M1 linear ubiquitination of LKB1 inhibits vascular endothelial cell injury in atherosclerosis through activation of AMPK

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机构： [1]Department of Cardiology, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, No. 16, Xiantong Road, Liantang Street, Luohu District, Shenzhen 518004, Guangdong, People’s Republic of China [2]Department of Encephalopathy, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen 518004, People’s Republic of China

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关键词： Atherosclerosis M1 linear ubiquitination Liver kinase B1 AMP-activated protein kinase Vascular endothelial cell injury

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Endothelial cell injury is confirmed to be the initial step in the atherosclerosis (AS) process. Here, we tried to elucidate the role of liver kinase B1 (LKB1) and adenosine phosphate protein kinase (AMPK) in modulating vascular endothelial cells (VECs) in AS. High-fat feed (HFD)-induced AS rat models were prepared and treated with AMPK activator A-769662 alone or combined with chloroquine. An analysis of VEC injury, inflammation response, and autophagy followed it. The M1 linear ubiquitination of LKB1 was assessed by co-immunoprecipitation. The interaction between LKB1 and AMPK was analyzed. Primary aortic VECs were isolated and induced by LPS to verify the effects of LKB1 and AMPK on VEC injury in AS. Activation of AMPK reduced the VEC injury and inflammatory response of VECs and promoted autophagy caused by AS. LKB1 could regulate the activation of AMPK in AS. M1 linear ubiquitination enhanced LKB1 activity and increased AMPK activation to protect against VEC injury in AS, which was validated by in vitro experiments. Our current study highlighted that M1 linear ubiquitination of LKB1 may induce the activation of LKB1 to activate AMPK, which inhibited VEC injury in AS.© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.

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出版当年[2022]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学

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第一作者机构： [1]Department of Cardiology, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, No. 16, Xiantong Road, Liantang Street, Luohu District, Shenzhen 518004, Guangdong, People’s Republic of China

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