دورية أكاديمية
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AMPKα is active in autophagy of endothelial cells in arsenic-induced vascular endothelial dysfunction by regulating mTORC1/p70S6K/ULK1.

التفاصيل البيبلوغرافية
العنوان: AMPKα is active in autophagy of endothelial cells in arsenic-induced vascular endothelial dysfunction by regulating mTORC1/p70S6K/ULK1.
المؤلفون: Xu Z; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Liu Q; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Li J; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Wang J; Institute for Prevention and Treatment of Sexually Transmitted Disease and AIDS, Center for Disease Control and Prevention of Hebei Province, Shijiazhuang, 050021, China., Yang Z; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Wang J; Department of Reproductive Medicine, Affiliated Hospital of Jining Medical College, Jining, 272000, China., Gao L; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Cheng J; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., He J; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Dong Y; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Guo X; Harbin Medical University Cancer Hospital, Harbin, 150081, China., Cui J; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China., Zhang W; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China. Electronic address: zhangwei@hrbmu.edu.cn.
المصدر: Chemico-biological interactions [Chem Biol Interact] 2024 Jan 25; Vol. 388, pp. 110832. Date of Electronic Publication: 2023 Dec 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.
مواضيع طبية MeSH: Arsenic*/toxicity , Cardiovascular Diseases*, Mice ; Animals ; Male ; Mechanistic Target of Rapamycin Complex 1 ; AMP-Activated Protein Kinases ; Endothelial Cells ; Ribosomal Protein S6 Kinases, 70-kDa ; Mice, Inbred C57BL ; Autophagy
مستخلص: Cardiovascular disease (CVD) is the most common cause of death, environmental factors, such as arsenic, playing an important role in the progress of CVD. Vascular endothelial dysfunction (VED) is a crucial early feature for CVD, inorganic arsenic (iAs) can induce autophagy in various cells. However, the role of endothelial autophagy has rarely been studied in VED triggered by arsenic. Total of one hundred and twenty healthy male C57BL/6J mice weighing 18-22 g were randomly divided into an arsenic-exposure group and a control group for 3, 6, 9, and 12 weeks. The results showed that, independent of the exposure period, autophagy markers of p-ATG16L1 levels and Beclin 1 contents in the aortic arch endothelium increased significantly compared with those of the corresponding control group. And different exposure duration decreased NO contents in the serum significantly. Combined with the histological changes that endothelial injury aggravated gradually with the increasing exposure period, suggesting that under exposure to iAs over 9 weeks, VED was remarkably induced, and consistant high levels of endothelial autophagy may play an important role. Additionally, levels of p-AMPKα/AMPKα increased significantly and p-mTORC1/mTORC1 levels decreased remarkably in the aortic arch endothelium. Then, a NaAsO 2 -induced-VED in vitro model was used to explore the mechanism of arsenic-induced endothelial autophagy. Similarly, p-AMPKα/AMPKα level significantly increased, and p-mTORC1/mTORC1 level remarkably decreased induced by 30 μmol/L NaAsO 2 in HUAECs. Further, an AMPK inhibitor (Compound C) pre-treatment prior to arsenic exposure reversed the increased autophagy level, and alleviated the endothelial dysfunction in HUVECs, as shown by the significant increase in the intracellular NO content and the cell vitality. Mechanistically, we revealed that AMPKα is active in autophagy of endothelial cells in arsenic-induced VED by regulating mTORC1/p70S6K/ULK1. The present study provide a new promising target for prevention and control arsenic-associated CVD.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wei Zhang reports financial support was provided by National Natural Science Foundation of China. None.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: AMP-activated protein kinase α (AMPKα); Arsenic; Autophagy; Endothelial dysfunction; Mammalian target of rapamycin (mTOR)
المشرفين على المادة: EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
N712M78A8G (Arsenic)
EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
تواريخ الأحداث: Date Created: 20231215 Date Completed: 20240115 Latest Revision: 20240115
رمز التحديث: 20240115
DOI: 10.1016/j.cbi.2023.110832
PMID: 38101599
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-7786
DOI:10.1016/j.cbi.2023.110832