Battino M, Littarru G P, Gorini A, Villa R F
Institute of Biochemistry, Faculty of Medicine, University of Ancona, Italy.
Neurochem Res. 1996 Dec;21(12):1505-14. doi: 10.1007/BF02533098.
The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration on respiratory chain features were studied in synaptic and non-synaptic mitochondrial populations from cerebral cortex and hippocampus of Macaca Fascicularis (Cynomolgus monkey). Enzymatic activity, cytochrome a + a3 content and turnover numbers of Complex IV, contents of Coenzyme Q10, of hydroperoxides and membrane fluidity were assessed in non-synaptic "perikaryal" and intra-synaptic "light" and "heavy" mitochondria isolated: (a) from the dopaminergic ascending terminal areas of cerebral cortex of monkeys treated p.o. with dihydroergocriptine at the dose of 2, 6 or 20 mg/kg/day for 52 weeks; (b) from the dopaminergic terminal areas of hippocampus of monkeys treated p.o. with dihydroergocriptine at the dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). Dihydroergocriptine administration moderately increased both cytochrome oxidase activity and cytochrome a + a3 content in "light" intra-synaptic mitochondria and hydroperoxides/CoQ10 ratio in all the types of mitochondria, as a consequence of the enhanced energy metabolism. The Parkinson's-like syndrome by MPTP changed the biochemical investigated parameters, affecting both directly the respiratory chain structures, i.e. by respiratory chain complexes inhibition and indirectly, i.e. by free radical mediated damages. MPTP administration negatively influenced Complex IV activity and Turnover Number of intra-synaptic mitochondria, without affecting the total cytochrome a + a3 amount. In all types of mitochondria and particularly on the "light" intra-synaptic ones, MPTP-induced lesion enhanced hydroperoxides/Coenzyme Q10 molar ratio due to the fall in Coenzyme Q10 levels and the concomitant increase in hydroperoxides. Dihydroergocriptine treatment appeared to be effective in MPTP-treated animals in improving those mitochondrial features that probably suffered free radical insults.
在食蟹猴（猕猴）大脑皮层和海马的突触和非突触线粒体群体中，研究了给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对呼吸链特征的影响。对分离出的非突触“胞体”线粒体、突触内“轻”线粒体和“重”线粒体评估了酶活性、细胞色素a + a3含量、复合物IV的周转数、辅酶Q10含量、氢过氧化物含量和膜流动性：（a）来自经口给予二氢麦角隐亭，剂量为2、6或20 mg/kg/天，持续52周的猴子大脑皮层多巴胺能上行终末区域；（b）来自在给予MPTP（静脉注射，0.3 mg/kg/天，共5天）诱导类帕金森综合征之前和期间，经口给予二氢麦角隐亭，剂量为12 mg/kg/天的猴子海马多巴胺能终末区域。由于能量代谢增强，给予二氢麦角隐亭适度增加了突触内“轻”线粒体中的细胞色素氧化酶活性和细胞色素a + a3含量，以及所有类型线粒体中的氢过氧化物/辅酶Q10比值。MPTP诱导的类帕金森综合征改变了所研究的生化参数，既直接影响呼吸链结构，即通过抑制呼吸链复合物，也间接影响，即通过自由基介导的损伤。给予MPTP对突触内线粒体的复合物IV活性和周转数有负面影响，但不影响细胞色素a + a3总量。在所有类型的线粒体中，特别是在突触内“轻”线粒体中，MPTP诱导的损伤由于辅酶Q10水平下降和氢过氧化物同时增加而提高了氢过氧化物/辅酶Q10摩尔比。二氢麦角隐亭治疗似乎对MPTP处理的动物有效，可改善那些可能遭受自由基损伤的线粒体特征。
