SIRT3-FOXO3a同种异构体形成核线粒体链接以对抗败血症诱导的小鼠心肌病氧化应激

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xun Luo, Zhengguang Geng, Han Zhang, Wenbo Chen, Junwen Zhang, Siyi Ming, Shiyuan Wang, Mingchun Wang, Haiyun Lei, Bao Fu, Xiaoyun Fu
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引用次数: 0

摘要

目的:败血症性心肌病(SIC)是败血症的严重并发症。SIC与蛋白质乙酰化之间的关系,特别是心肌细胞亚细胞结构中乙酰化和去乙酰化之间的平衡,以及核-线粒体协调如何维持标准的抗氧化应激能力,目前尚不清楚。本研究重点探讨Sirtuin 3 (SIRT3)与叉头盒O3a (FOXO3a)相互作用形成的核线粒体调控机制。结果:在体内,野生型CLP(盲肠结扎和穿刺)小鼠的SIC标记在72h (CLP72h)时显著升高,而在CLP72h+oeSIRT3小鼠中部分逆转。CLP72h小鼠的线粒体面积、纵横比和mtDNA拷贝数显著减少。超声心动图显示心功能明显受损。Western blotting显示,CLP72h小鼠细胞核和线粒体长型SIRT3、细胞核长型和线粒体短型FOXO3a、线粒体超氧化物歧化酶2 (SOD2)显著降低,乙酰化显著升高。在体外,oeSIRT3保留了细胞核FOXO3a的定位和线粒体膜电位,CLP72h+oeSIRT3小鼠的氧化应激显著降低。长链SIRT3在SIC中起着至关重要的去乙酰化作用,并通过FOXO3a部分影响SOD2。创新:本研究探讨了不同SIRT3和FOXO3a亚型通过核-线粒体动态调控对抗SIC氧化应激的作用。结论:本研究强调SIRT3-FOXO3a轴在SIC过程中通过核-线粒体网络增强线粒体抗氧化能力的关键作用,为SIC的分子机制和潜在的治疗策略提供了新的见解。Antioxid。氧化还原信号:00000 - 00000。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SIRT3-FOXO3a Isoforms Forge Nuclear-Mitochondrial Links to Combat Sepsis-Induced Cardiomyopathy Oxidative Stress in Mice.

Aims: Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis. The relationship between SIC and protein acetylation, particularly the balance between acetylation and deacetylation in cardiomyocyte subcellular structures, as well as how nuclear-mitochondrial coordination maintains standard antioxidant stress capacity, remains unclear. This study focused on exploring the nuclear-mitochondrial regulatory mechanisms formed by the interplay of Sirtuin 3 (SIRT3) and Forkhead box O3a (FOXO3a). Results: In vivo, SIC markers increased significantly in wild-type CLP (Cecal Ligation and Puncture) mice at 72 h (CLP72h) but were partially reversed in CLP72h+oeSIRT3 mice. CLP72h mice exhibited significantly reduced mitochondrial area, aspect ratio, and mtDNA copy number. Echocardiography revealed significantly impaired cardiac function. Western blotting showed significantly decreased nuclear and mitochondrial long-form SIRT3, nuclear long-form and mitochondrial short-form FOXO3a, and mitochondrial superoxide dismutase 2 (SOD2), with significantly increased acetylation in CLP72h mice. In vitro, oeSIRT3 preserved nuclear FOXO3a localization and mitochondrial membrane potential, with CLP72h+oeSIRT3 mice showing significantly reduced oxidative stress. The long form of SIRT3 plays a crucial deacetylation role in SIC and influences SOD2 partially through FOXO3a. Innovation: This study explored the roles of different SIRT3 and FOXO3a isoforms in combating oxidative stress in SIC through dynamic nucleus-mitochondrial regulation. Conclusion: This study underscores the critical role of the SIRT3-FOXO3a axis in enhancing mitochondrial antioxidant capacity through a nuclear-mitochondrial network during SIC, offering new insights into molecular mechanisms and potential therapeutic strategies for SIC. Antioxid. Redox Signal. 00, 000-000.

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来源期刊
Antioxidants & redox signaling
Antioxidants & redox signaling 生物-内分泌学与代谢
CiteScore
14.10
自引率
1.50%
发文量
170
审稿时长
3-6 weeks
期刊介绍: Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology
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