Dynamin-related protein 1属于动力蛋白GTP酶超家族,是线粒体分裂体系的组成成分,在线粒体分裂中具有重要作用。在不同物种中,dynamin-related protein 1在与多种分子相互作用后,可以定位于线粒体并组装成高级结构,引起膜的收缩和分裂...Dynamin-related protein 1属于动力蛋白GTP酶超家族,是线粒体分裂体系的组成成分,在线粒体分裂中具有重要作用。在不同物种中,dynamin-related protein 1在与多种分子相互作用后,可以定位于线粒体并组装成高级结构,引起膜的收缩和分裂。Dynamin-related protein 1功能的消失会增强线粒体的融合和线粒体之间的连通性。Dynamin-related protein 1在细胞凋亡等多种细胞功能中也具有重要作用。展开更多
Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynami...Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 （Drp1） can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 （depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day）. Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.展开更多
骨骼肌是机体重要的代谢器官,其代谢紊乱可导致糖尿病和肌萎缩等疾病。线粒体作为代谢调控的核心细胞器,其动态平衡(融合/分裂)能够通过调控骨骼肌的能量稳态,直接影响其生理功能。发动蛋白相关蛋白1(dynamin-related protein 1,Drp1)...骨骼肌是机体重要的代谢器官,其代谢紊乱可导致糖尿病和肌萎缩等疾病。线粒体作为代谢调控的核心细胞器,其动态平衡(融合/分裂)能够通过调控骨骼肌的能量稳态,直接影响其生理功能。发动蛋白相关蛋白1(dynamin-related protein 1,Drp1)是调控线粒体分裂的关键蛋白,在骨骼肌线粒体中高度表达。近年来研究显示,Drp1通过调控线粒体分裂,参与自噬、凋亡等多种细胞途径,在骨骼肌葡萄糖、脂质及蛋白质代谢稳态中发挥核心作用。因此,Drp1功能异常在多种代谢性疾病的发生与发展中具有重要研究意义,特别是在糖尿病和肌萎缩中可能成为潜在的治疗靶点。本文综述了Drp1的分子特征及其在骨骼肌代谢调控中的作用机制,并探讨其在病理生理状态下的调控网络,为靶向Drp1的治疗研究提供参考资料。展开更多
文摘Dynamin-related protein 1属于动力蛋白GTP酶超家族,是线粒体分裂体系的组成成分,在线粒体分裂中具有重要作用。在不同物种中,dynamin-related protein 1在与多种分子相互作用后,可以定位于线粒体并组装成高级结构,引起膜的收缩和分裂。Dynamin-related protein 1功能的消失会增强线粒体的融合和线粒体之间的连通性。Dynamin-related protein 1在细胞凋亡等多种细胞功能中也具有重要作用。
基金supported by the Natural Science Foundation of Shandong Province of China,No.ZR2015HM023a grant from the Science and Technology Plan Project of Shinan District of Qingdao City of China,No.2016-3-029-YY
文摘Electroacupuncture preconditioning at acupoint Baihui （GV20） can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 （Drp1） can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 （depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day）. Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.
文摘骨骼肌是机体重要的代谢器官,其代谢紊乱可导致糖尿病和肌萎缩等疾病。线粒体作为代谢调控的核心细胞器,其动态平衡(融合/分裂)能够通过调控骨骼肌的能量稳态,直接影响其生理功能。发动蛋白相关蛋白1(dynamin-related protein 1,Drp1)是调控线粒体分裂的关键蛋白,在骨骼肌线粒体中高度表达。近年来研究显示,Drp1通过调控线粒体分裂,参与自噬、凋亡等多种细胞途径,在骨骼肌葡萄糖、脂质及蛋白质代谢稳态中发挥核心作用。因此,Drp1功能异常在多种代谢性疾病的发生与发展中具有重要研究意义,特别是在糖尿病和肌萎缩中可能成为潜在的治疗靶点。本文综述了Drp1的分子特征及其在骨骼肌代谢调控中的作用机制,并探讨其在病理生理状态下的调控网络,为靶向Drp1的治疗研究提供参考资料。
