1-Methyl-4-phenylpyridinium (MPP+) is a mitochondrial Complex I inhibitor and is frequently used to investigate the pathological degeneration of neurons associated with Parkinson's disease (PD). In vitro, extracellular concentration of glucose is one of the most critical factors in establishing the vulnerability of neurons to MPP+ toxicity. While glucose is the primary energy fuel for the brain, central nervous system (CNS) neurons can also take up and utilize other metabolic intermediates for energy. In this study, we compared various monosaccharides, disaccharides, nutritive/non-nutritive sugar alcohols, glycolytic and gluconeogenic metabolic intermediates for their cytoprotection against MPP+ in murine brain neuroblastoma cells. Several monosaccharides were effective against MMP+ (500 microM) including glucose, fructose and mannose, which restored cell viability to 109 +/- 5%, 70 +/- 5%, 99 +/- 3% of live controls, respectively. Slight protective effects were observed in the presence of 3-phosphoglyceric acid and glucose-6-phosphate; however, no protective effects were exhibited by galactose, sucrose, sorbitol, mannitol, glycerol or various gluconeogenic and ketogenic amino acids. On the other hand, fructose 1,6 bisphosphate and gluconeogenic energy intermediates [pyruvic acid, malic acid and phospho(enol)pyruvate (PEP)] were neuroprotective against MPP+. The gluconeogenic intermediates elevated intracellular levels of ATP and reduced propidium iodide (PI) nucleic acid staining to live controls, but did not alter the MPP(+)-induced loss of mitochondrial O2 consumption. These data indicate that malic acid, pyruvic acid and PEP contribute to anaerobic substrate level phosphorylation. The use of hydrazine sulfate to impede gluconeogenesis through PEP carboxykinase (PEPCK) inhibition heightened the protective effects of energy substrates possibly due to attenuated ATP demands from pyruvate carboxylase (PC) activity and pyruvate mitochondrial transport. It was concluded from these studies that several metabolic intermediates are effective in fueling anaerobic glycolysis during mitochondrial inhibition by MPP+.

中文翻译：

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糖酵解和糖异生在神经母细胞瘤细胞针对1-甲基4-苯基吡啶鎓离子毒性的细胞保护中的作用。

1-甲基-4-苯基吡啶鎓（MPP +）是线粒体复合物I抑制剂，经常用于研究与帕金森氏病（PD）相关的神经元的病理变性。在体外，葡萄糖的细胞外浓度是确定神经元对MPP +毒性的脆弱性的最关键因素之一。葡萄糖是大脑的主要能源，而中枢神经系统（CNS）神经元也可以吸收并利用其他代谢中间体来获取能量。在这项研究中，我们比较了各种单糖，二糖，营养/非营养糖醇，糖酵解和糖异生代谢中间体对小鼠脑神经母细胞瘤细胞中MPP +的细胞保护作用。几种单糖对MMP +（500 microM）有效，包括葡萄糖，果糖和甘露糖，使细胞活力分别恢复至活体对照的109 +/- 5％，70 +/- 5％，99 +/- 3％。在3-磷酸甘油酸和6-磷酸葡萄糖的存在下，观察到了轻微的保护作用。然而，半乳糖，蔗糖，山梨糖醇，甘露醇，甘油或各种糖异生和生酮氨基酸均未表现出保护作用。另一方面，果糖1,6二磷酸和糖异生能中间体[丙酮酸，苹果酸和磷酸（烯醇）丙酮酸（PEP）]对MPP +具有神经保护作用。糖异生中间体提高了细胞内ATP的水平，并降低了碘化丙锭（PI）核酸染色的活细胞，但没有改变MPP（+）引起的线粒体O2消耗的损失。这些数据表明苹果酸，丙酮酸和PEP有助于厌氧底物水平的磷酸化。硫酸肼通过PEP羧激酶（PEPCK）抑制作用来阻止糖异生的作用增强了能量底物的保护作用，这可能是由于丙酮酸羧化酶（PC）活性和丙酮酸线粒体运输对ATP的需求减弱所致。从这些研究得出的结论是，在MPP +抑制线粒体过程中，几种代谢中间体可有效促进厌氧糖酵解。