Virmani M A, Biselli R, Spadoni A, Rossi S, Corsico N, Calvani M, Fattorossi A, De Simone C, Arrigoni-Martelli E
Sigma-Tau, Pomezia, Rome.
Pharmacol Res. 1995 Dec;32(6):383-9. doi: 10.1016/s1043-6618(05)80044-1.
The mechanism for the pathological increase in cell death in various disease states e.g. HIV immunodefficiency or even ageing or Alzheimer's disease, occurs by complex and as yet undefined mechanism(s) related to immunological, virological or biochemical disturbances (i.e. energy depletion, oxidative stress, increased protein degradation). We have studied mitochondrial uncoupling or inhibitor toxicity on neurones at the cellular level and at the mitochondrial level using rhodamine (Rh123) and 10-nonylacridine orange (NAO) fluorescence with confocal microscopy. Blockade of the mitochondrial chain complexes at various points was studied. The possible protective effects of the compound L-carnitine, which plays a central role in mitochondrial function, was tested in this form of neurotoxicity. It appears that L-carnitine and its acetylated form, acetyl-L-carnitine, can attenuate the cell damage, as assessed by lactate dehydrogenase (LDH) release, evoked by the uncoupler, p-(trifluoromethoxy)phenylhdyrazone (FCCP), or by the inhibitors, 3-nitropropionic acid (3-NPA) or rotenone. Further, the FCCP-induced inhibition of Rh123 uptake was antagonized by the preincubation of cells with L-carnitine. Since such neurotoxic mechanisms may be operating in the various pathological forms of myotoxicity and neurotoxicity, these observations suggest potential for a therapeutic approach.
在各种疾病状态下，如HIV免疫缺陷、甚至衰老或阿尔茨海默病，细胞死亡病理性增加的机制是通过与免疫、病毒或生化紊乱（即能量耗竭、氧化应激、蛋白质降解增加）相关的复杂且尚未明确的机制发生的。我们使用罗丹明（Rh123）和10-壬基吖啶橙（NAO）荧光结合共聚焦显微镜，在细胞水平和线粒体水平研究了线粒体解偶联或抑制剂对神经元的毒性。研究了在不同位点对线粒体呼吸链复合物的阻断作用。在这种神经毒性形式中，测试了在 mitochondrial function中起核心作用的化合物L-肉碱的可能保护作用。似乎L-肉碱及其乙酰化形式乙酰-L-肉碱可以减轻由解偶联剂对-(三氟甲氧基)苯腙（FCCP）或抑制剂3-硝基丙酸（3-NPA）或鱼藤酮引起的、通过乳酸脱氢酶（LDH）释放评估的细胞损伤。此外，L-肉碱预孵育细胞可拮抗FCCP诱导的Rh123摄取抑制。由于这种神经毒性机制可能在各种形式的肌毒性和神经毒性的病理过程中起作用，这些观察结果提示了一种治疗方法的潜力。
