Suppr超能文献

褪黑素后处理通过调节 SIRT3 依赖性的线粒体自噬和线粒体动力学来减轻缺氧/复氧损伤。

Melatonin postconditioning ameliorates anoxia/reoxygenation injury by regulating mitophagy and mitochondrial dynamics in a SIRT3-dependent manner.

机构信息

Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People's Republic of China.

Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Eur J Pharmacol. 2021 Aug 5;904:174157. doi: 10.1016/j.ejphar.2021.174157. Epub 2021 May 8.

Abstract

Ischaemia/reperfusion (I/R) injury is accompanied by excessive mitochondrial autophagy (mitophagy) and an imbalance in mitochondrial dynamics. Melatonin has been reported to alleviate I/R injury by regulating mitophagy and mitochondrial dynamics. However, the underlying mechanism associated with this activity is not fully understood. The goal of the present study was to investigate whether and how melatonin administration at the beginning of reoxygenation exerts protective effects by regulating mitophagy and mitochondrial dynamics. H9c2 cells were transfected with sirtuin 3 (SIRT3)-targeting siRNA and then subjected to anoxia/reoxygenation (A/R) injury, with melatonin (150 μM) administered at the onset of reoxygenation. Biomarkers related to cellular apoptosis, oxidative stress, mitochondrial function, mitophagy and mitochondrial dynamics were assessed, and the expression and activity of SIRT3 was also measured. Mitochondrial fission and mitophagy were activated after A/R injury and were accompanied by cellular apoptosis, oxidative stress, and mitochondrial dysfunction. However, melatonin postconditioning inhibited excessive mitochondrial fission and mitophagy, promoted mitochondrial fusion, restored mitochondrial function and reduced cellular apoptosis, and the mitophagy inhibitor 3-methyladenine (3-MA) also attenuated A/R-induced apoptosis. Moreover, the A/R-induced decreases in SIRT3 and manganese superoxide dismutase (SOD2) activities were ameliorated by melatonin. However, SIRT3 silencing abolished the beneficial effects of melatonin, eliminated the inhibitory effects of melatonin on mitochondrial fission and mitophagy, and reversed the melatonin-induced increase in SOD2 activity. These results indicate that melatonin postconditioning protects H9c2 cells from A/R injury by inhibiting excessive mitophagy and maintaining the balance of mitochondrial fission and fusion in a SIRT3-dependent manner.

摘要

缺血/再灌注(I/R)损伤伴随着过度的线粒体自噬(mitophagy)和线粒体动力学失衡。褪黑素已被报道通过调节线粒体自噬和线粒体动力学来减轻 I/R 损伤。然而,其活性相关的潜在机制尚不完全清楚。本研究旨在探讨褪黑素在再复氧开始时给药是否以及如何通过调节线粒体自噬和线粒体动力学发挥保护作用。H9c2 细胞用 SIRT3 靶向 siRNA 转染,然后进行缺氧/复氧(A/R)损伤,在再复氧开始时给予褪黑素(150μM)。评估与细胞凋亡、氧化应激、线粒体功能、线粒体自噬和线粒体动力学相关的生物标志物,并测量 SIRT3 的表达和活性。A/R 损伤后线粒体分裂和线粒体自噬被激活,并伴有细胞凋亡、氧化应激和线粒体功能障碍。然而,褪黑素后处理抑制了过度的线粒体分裂和自噬,促进了线粒体融合,恢复了线粒体功能并减少了细胞凋亡,并且线粒体自噬抑制剂 3-甲基腺嘌呤(3-MA)也减轻了 A/R 诱导的细胞凋亡。此外,褪黑素改善了 A/R 引起的 SIRT3 和锰超氧化物歧化酶(SOD2)活性降低。然而,SIRT3 沉默消除了褪黑素的有益作用,消除了褪黑素对线粒体分裂和自噬的抑制作用,并逆转了褪黑素诱导的 SOD2 活性增加。这些结果表明,褪黑素后处理通过抑制过度的线粒体自噬并以 SIRT3 依赖的方式维持线粒体分裂和融合的平衡来保护 H9c2 细胞免受 A/R 损伤。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验