Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury.
Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury.
复制标题
鸢尾素在肺缺血/再灌注损伤期间保护线粒体功能。
DOI：
10.1126/scitranslmed.aao6298
复制
发表时间：
2017-11-29
影响因子：
17.1
通讯作者：
Zeng C
中科院分区：
文献类型：
--
作者：
Chen K;Xu Z;Liu Y;Wang Z;Li Y;Xu X;Chen C;Xia T;Liao Q;Yao Y;Zeng C;He D;Yang Y;Tan T;Yi J;Zhou J;Zhu H;Ma J;Zeng C
肢体远端缺血预处理（RIPC）是一种有效的保护缺血再灌注（IR）所致多器官损伤的方法。许多研究都集中在确定肌肉和RIPC介导的器官保护之间的相互作用的内分泌机制。我们报告说，RIPC释放鸢尾素，肌细胞因子来源于细胞外部分的纤连蛋白结构域5蛋白（FNDC5）在骨骼肌，以防止肺损伤。患有新生儿呼吸窘迫综合征的人类患者显示血清中的鸢尾素浓度降低和支气管肺泡灌洗液中的鸢尾素浓度增加，表明在生理应激下鸢尾素从循环转移到肺。在小鼠中，应用短暂的缺血预处理刺激释放鸢尾素进入循环，并将鸢尾素转移到IR损伤的肺。鸢尾素通过脂筏介导的内吞作用进入肺泡细胞并靶向线粒体。鸢尾素和线粒体解偶联蛋白2（UCP2）之间的相互作用可以防止IR诱导的氧化应激和线粒体功能的保护。动物模型研究表明，静脉注射外源性鸢尾素可以通过改善线粒体功能来防止IR诱导的肺损伤，而在UCP 2缺陷小鼠或存在UCP 2抑制剂的情况下，鸢尾素的保护作用会受到损害。这些结果表明，鸢尾素是促进RIPC介导的肺保护的肌因子。靶向鸢尾素在线粒体中的作用为肺IR损伤提供了潜在的治疗干预。
Limb remote ischemic preconditioning (RIPC) is an effective means of protection against ischemia/reperfusion (IR)–induced injury to multiple organs. Many studies are focused on identifying endocrine mechanisms that underlie the cross-talk between muscle and RIPC-mediated organ protection. We report that RIPC releases irisin, a myokine derived from the extracellular portion of fibronectin domain–containing 5 protein (FNDC5) in skeletal muscle, to protect against injury to the lung. Human patients with neonatal respiratory distress syndrome show reduced concentrations of irisin in the serum and increased irisin concentrations in the bronchoalveolar lavage fluid, suggesting transfer of irisin from circulation to the lung under physiologic stress. In mice, application of brief periods of ischemia preconditioning stimulates release of irisin into circulation and transfer of irisin to the lung subjected to IR injury. Irisin, via lipid raft–mediated endocytosis, enters alveolar cells and targets mitochondria. Interaction between irisin and mitochondrial uncoupling protein 2 (UCP2) allows for prevention of IR-induced oxidative stress and preservation of mitochondrial function. Animal model studies show that intravenous administration of exogenous irisin protects against IR-induced injury to the lung via improvement of mitochondrial function, whereas in UCP2-deficient mice or in the presence of a UCP2 inhibitor, the protective effect of irisin is compromised. These results demonstrate that irisin is a myokine that facilitates RIPC-mediated lung protection. Targeting the action of irisin in mitochondria presents a potential therapeutic intervention for pulmonary IR injury.
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影响因子：
2.2
作者：
Fukushima, Yaeko;Kurose, Satoshi;Shinno, Hiromi;Cao Thi Thu, Ha;Tamanoi, Atsuko;Tsutsumi, Hiromi;Hasegawa, Takaaki;Nakajima, Toshiaki;Kimura, Yutaka
通讯作者：
Kimura, Yutaka
DOI：
10.1007/978-1-4939-0685-7_20
发表时间：
2014-01-01
期刊：
SHOTGUN PROTEOMICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Castro-Gamero, Angel Mauricio;Izumi, Clarice;Rosa, Jose Cesar
通讯作者：
Rosa, Jose Cesar
影响因子：
4.8
作者：
Ambrosio, G;Tritto, I
通讯作者：
Tritto, I
DOI：
10.1016/j.bbamcr.2016.04.013
发表时间：
2016-10-01
影响因子：
5.1
作者：
Bouillaud, Frederic;Alves-Guerra, Marie-Clotilde;Ricquier, Daniel
通讯作者：
Ricquier, Daniel
影响因子：
4.3
作者：
Gill, Rabia;Kuriakose, Robin;Kukreja, Rakesh C.
通讯作者：
Kukreja, Rakesh C.