University of Buenos Aires, School of Pharmacy and Biochemistry, Physical Chemistry Division, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET), Buenos Aires, Argentina.
University of Buenos Aires, School of Pharmacy and Biochemistry, Physical Chemistry Division, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET), Buenos Aires, Argentina.
Free Radic Biol Med. 2019 May 1;135:274-282. doi: 10.1016/j.freeradbiomed.2019.03.001. Epub 2019 Mar 9.
Mitochondrial dysfunction named complex I syndrome was observed in striatum mitochondria of rotenone treated rats (2 mg rotenone/kg, i. p., for 30 or 60 days) in an animal model of Parkinson disease. After 60 days of rotenone treatment, the animals showed: (a) 6-fold increased bradykinesia and 60% decreased locomotor activity; (b) 35-34% decreases in striatum O uptake and in state 3 mitochondrial respiration with malate-glutamate as substrate; (c) 43-57% diminished striatum complex I activity with 60-71% decreased striatum mitochondrial NOS activity, determined both as biochemical activity and as functional activity (by the NO inhibition of active respiration); (d) 34-40% increased rates of mitochondrial O and HO productions and 36-46% increased contents of the products of phospholipid peroxidation and of protein oxidation; and (e) 24% decreased striatum mitochondrial content, likely associated to decreased NO-dependent mitochondrial biogenesis. Intermediate values were observed after 30 days of rotenone treatment. Frontal cortex tissue and mitochondria showed similar but less marked changes. Rotenone-treated rats showed mitochondrial complex I syndrome associated with cellular oxidative stress in the dopaminergic brain areas of striatum and frontal cortex, a fact that describes the high sensitivity of mitochondrial complex I to inactivation by oxidative reactions.
在帕金森病动物模型中，用鱼藤酮（2mg/kg，腹腔注射，30 或 60 天）处理大鼠纹状体的线粒体，观察到线粒体功能障碍，命名为复合物 I 综合征。在鱼藤酮处理 60 天后，动物表现出：（a）运动徐缓增加 6 倍，运动活性降低 60%；（b）纹状体 O 摄取和以苹果酸-谷氨酸为底物的线粒体呼吸状态 3 降低 35-34%；（c）纹状体复合物 I 活性降低 43-57%，纹状体线粒体 NOS 活性降低 60-71%，这两个酶的活性通过测定活性呼吸的 NO 抑制来确定；（d）线粒体 O 和 HO 生成率增加 34-40%，磷脂过氧化和蛋白质氧化产物的含量增加 36-46%；（e）纹状体线粒体含量降低 24%，可能与 NO 依赖性线粒体生物发生减少有关。在鱼藤酮处理 30 天后观察到中间值。前额皮质组织和线粒体显示出类似但程度较轻的变化。鱼藤酮处理的大鼠表现出与多巴胺能脑区纹状体和前额皮质细胞氧化应激相关的线粒体复合物 I 综合征，这一事实描述了线粒体复合物 I 对氧化反应失活的高度敏感性。
