PMID- 36563952 OWN - NLM STAT- MEDLINE DCOM- 20230117 LR - 20231213 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 940 DP - 2023 Feb 5 TI - Cyclophilin D-mediated angiotensin II-induced NADPH oxidase 4 activation in endothelial mitochondrial dysfunction that can be rescued by gallic acid. PG - 175475 LID - S0014-2999(22)00736-1 [pii] LID - 10.1016/j.ejphar.2022.175475 [doi] AB - Vascular endothelial dysfunction plays a central role in the most dreadful human diseases, including stroke, tumor metastasis, and the coronavirus disease 2019 (COVID-19). Strong evidence suggests that angiotensin II (Ang II)-induced mitochondrial dysfunction is essential for endothelial dysfunction pathogenesis. However, the precise molecular mechanisms remain obscure. Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2 and NADPH oxidase 4 (NOX 4) expression treated by Ang II. Interestingly, we first found that Ang II-induced NOX 4 binds with Poldip 2 was dependent on cyclophilin D (CypD). CypD knockdown (KD) significantly inhibited the binding of NOX 4 to Poldip 2, and mitochondrial ROS generation in human umbilical vein endothelial cells (HUVECs). Similar results were also found in cyclosporin A (CsA) treated HUVECs. Our previous study suggested a crosstalk between extracellular regulated protein kinase (ERK) phosphorylation and CypD expression, and gallic acid (GA) inhibited mitochondrial dysfunction in neurons depending on regulating the ERK-CypD axis. Here, we confirmed that GA inhibited Ang II-induced NOX 4 activation and mitochondrial dysfunction via ERK/CypD/NOX 4/Poldip 2 pathway, which provide novel mechanistic insight into CypD act as a key regulator of the NOX 4/Poldip 2 axis in Ang II-induced endothelial mitochondrial dysfunction and GA might be beneficial in the treatment of wide variety of diseases, such as COVID-19, which is worthy further research. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Sun, Jing AU - Sun J AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China; Department of Traditional Chinese Medicine & Pharmacy, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: sjyancheng@ujs.edu.cn. FAU - Liu, Yunxi AU - Liu Y AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Chen, Chen AU - Chen C AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Quarm, Anthony Kwesi AU - Quarm AK AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Xi, Siyu AU - Xi S AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Sun, Tingkai AU - Sun T AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Zhang, Dingqi AU - Zhang D AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Qian, Jinjun AU - Qian J AD - Department of Neurology, The Fourth People's Hospital of Zhenjiang, Zhenjiang, 212001, PR China. FAU - Ding, Hongqun AU - Ding H AD - Department of Clinical Laboratory Diagnostics, School of Medicine, Jiangsu University, Zhenjiang, 212013, PR China. FAU - Gao, Jing AU - Gao J AD - Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; Effective & Toxicity Monitoring Innovative Practice Center for Food Pharmaceutical Specialty, Jiangsu University, Zhenjiang, 212013, PR China. LA - eng PT - Journal Article DEP - 20221221 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - EC 1.6.3.- (NADPH Oxidase 4) RN - 11128-99-7 (Angiotensin II) RN - 0 (Reactive Oxygen Species) RN - 0 (Peptidyl-Prolyl Isomerase F) RN - EC 1.6.3.- (NADPH Oxidases) RN - 632XD903SP (Gallic Acid) SB - IM MH - Humans MH - NADPH Oxidase 4/metabolism MH - Angiotensin II/pharmacology/metabolism MH - Reactive Oxygen Species/metabolism MH - Peptidyl-Prolyl Isomerase F/metabolism/pharmacology MH - NADPH Oxidases/metabolism MH - Oxidative Stress MH - Gallic Acid/pharmacology MH - *COVID-19/metabolism MH - Mitochondria MH - *Vascular Diseases MH - Human Umbilical Vein Endothelial Cells OTO - NOTNLM OT - Angiotensin II (Ang II) OT - Cyclophilin D (CypD) OT - Endothelial mitochondrial dysfunction OT - Gallic acid (GA) OT - NADPH oxidase 4 (NOX 4) OT - Polymerase delta-interacting protein 2 (Poldip 2) COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/12/24 06:00 MHDA- 2023/01/18 06:00 CRDT- 2022/12/23 19:17 PHST- 2022/07/12 00:00 [received] PHST- 2022/11/21 00:00 [revised] PHST- 2022/12/16 00:00 [accepted] PHST- 2022/12/24 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] PHST- 2022/12/23 19:17 [entrez] AID - S0014-2999(22)00736-1 [pii] AID - 10.1016/j.ejphar.2022.175475 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Feb 5;940:175475. doi: 10.1016/j.ejphar.2022.175475. Epub 2022 Dec 21.