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Cell：发现新的细胞超氧生成事件
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Cell：发现新的细胞超氧生成事件 [转自 生物谷] 来源 科技部基础研究司 活性氧族（reactive oxygen species, ROS）是含氧并具有高反应活性的一类自由基或分子，其中超氧阴离子是一种高活性氧自由基，并且是细胞内ROS的最初生成形式，广泛参与细胞信号调节、代谢、生存和凋亡，而氧化应激是衰老和多种重大疾病如心肌梗死、脑卒中、糖尿病、老年痴呆症等重要机制之一。 在科技部973计划等的资助下，北京大学分子医学研究所程和平教授研究组与合作者为共同第一作者和共同责任作者的论文“单个线粒体超氧炫”，于7月25日在《细胞》（Cell）杂志以配图 “Featured Article”形式发表。 研究发现一种新的细胞超氧生成事件，并命名为“超氧炫”（superoxide flashes）。超氧炫是细胞内（含102-104个线粒体）单个线粒体中超氧信号的瞬时爆发现象，这是首次在活体细胞中观测到局部、间歇性、量子化超氧的产生。超氧炫为线粒体膜通透性转运孔道(mPTP)开放所触发，与线粒体电子传递链活性密切相关。上述发现是基于发明了一种新颖的高特异性超氧指示剂，即基因编码的、定位于线粒体的可用于实时测量的荧光蛋白。 上述工作对自由基和线粒体研究领域有三方面的意义，一是找到了新的ROS信号指示剂，二是超氧炫可作为氧化应激相关疾病的生物标记物，三是对生理和病理状况下mPTP和电子传递链功能有了新认识。 Cell，Vol 134, 279-290，Wang Wang，Heping Cheng Superoxide Flashes in Single Mitochondria Wang Wang,1, Huaqiang Fang,4 Linda Groom,5 Aiwu Cheng,2 Wanrui Zhang,4 Jie Liu,4 Xianhua Wang,4 Kaitao Li,4 Peidong Han,4 Ming Zheng,4 Jinhu Yin,3 Weidong Wang,3 Mark P. Mattson,2 Joseph P.Y. Kao,6 Edward G. Lakatta,1 Shey-Shing Sheu,5 Kunfu Ouyang,7 Ju Chen,7 Robert T. Dirksen,5 and Heping Cheng4, 1 Laboratories of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA 2 Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA 3 Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA 4 Institute of Molecular Medicine and National Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China 5 Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA 6 Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA 7 Department of Medicine, University of California, San Diego, CA 92093, USA Summary In quiescent cells, mitochondria are the primary source of reactive oxygen species (ROS), which are generated by leakiness of the electron transport chain (ETC). High levels of ROS can trigger cell death, whereas lower levels drive diverse and important cellular functions. We show here by employing a newly developed mitochondrial matrix-targeted superoxide indicator, that individual mitochondria undergo spontaneous bursts of superoxide generation, termed “superoxide flashes.” Superoxide flashes occur randomly in space and time, exhibit all-or-none properties, and provide a vital source of superoxide production across many different cell types. Individual flashes are triggered by transient openings of the mitochondrial permeability transition pore stimulating superoxide production by the ETC. Furthermore, we observe a flurry of superoxide flash activity during reoxygenation of cardiomyocytes after hypoxia, which is inhibited by the cardioprotective compound adenosine. We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases. |
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