Transferring Xenogenic Mitochondria Provides Neural Protection Against Ischemic Stress in Ischemic Rat Brains
Transferring Xenogenic Mitochondria Provides Neural Protection Against Ischemic Stress in Ischemic Rat Brains
复制标题
DOI：
10.3727/096368915x689785
复制
发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Su, Hong-Lin
中科院分区：
文献类型：
--
作者：
Huang, Po-Jui;Kuo, Chi-Chung;Su, Hong-Lin
转移外源线粒体对受损的心、肝、肺组织有治疗作用。这种保护作用是否需要外源线粒体在宿主细胞中共生尚不清楚。在这里，来自仓鼠细胞系的异种线粒体被应用于缺血大鼠大脑和大鼠原代皮质神经元。分离的仓鼠线粒体，无论是通过局部脑内注射还是全身动脉下注射，都显著恢复了脑缺血大鼠的运动能力。外源性线粒体可减轻脑梗塞面积和神经细胞死亡。虽然在神经元和星形胶质细胞中可以观察到内在化的线粒体，但线粒体内在化的低效率并不能完全解释处理后神经细胞的高挽救率。我们进一步说明，破坏线粒体中的电子传递或ATPase合成酶显著减弱了这种保护作用，表明完整的呼吸活动对于线粒体的神经保护作用是必不可少的。这些结果强调，非共生的胞外线粒体可以为中枢神经系统的急性损伤性缺血应激提供有效的细胞防御。
Transferring exogenous mitochondria has therapeutic effects on damaged heart, liver, and lung tissues. Whether this protective effect requires the symbiosis of exogenous mitochondria in host cells remains unknown. Here xenogenic mitochondria derived from a hamster cell line were applied to ischemic rat brains and rat primary cortical neurons. Isolated hamster mitochondria, either through local intracerebral or systemic infra-arterial injection, significantly restored the motor performance of brain-ischemic rats. The brain infarct area and neuronal cell death were both attenuated by the exogenous mitochondria. Although internalized mitochondria could be observed in neurons and astrocytes, the low efficacy of mitochondrial internalization could not completely account for the high rate of rescue of the treated neural cells. We further illustrated that disrupting electron transport or ATPase synthase in mitochondria significantly attenuated the protective effect, suggesting that intact respiratory activity is essential for the mitochondrial potency on neural protection. These results emphasize that nonsymbiotic extracellular mitochondria can provide an effective cell defense against acute injurious ischemic stress in the central nervous system.