Erecinńska M, Nelson D, Vanderkooi J M
Department of Pharmacology, University of Pennsylvania, Philadelphia, USA.
J Neurochem. 1995 Dec;65(6):2699-705. doi: 10.1046/j.1471-4159.1995.65062699.x.
The effects of nitroprusside and S-nitrosocysteine, compounds that generate nitric oxide (NO), on synaptosomal energy-producing pathways and energy level were investigated. The decrease in respiration was much faster and more pronounced with S-nitrosocysteine than with nitroprusside. S-Nitrosocysteine, at 10 microM, inhibited by 80% respiration with glucose and succinate (plus rotenone) in intact synaptosomes and with ascorbate/cytochrome c in broken preparations. Oxygenated hemoglobin reversed and/or prevented the inhibition, whereas glutathione (GSH) prolonged it. Under aerobic conditions, the synaptosomal energy level (creatine phosphate/creatine and ATP/ADP ratios) was reduced by the presence of S-nitrosocysteine, whereas lactate generation was enhanced. The effects on energy parameters were greater at 5 min than at 15 min of incubation and were more pronounced in the presence of GSH. Under strictly anaerobic conditions, lactate production was reduced by the NO-generating compounds in a concentration-dependent manner. It is concluded that (a) inhibition of oxidative phosphorylation by NO leads to a fall in the synaptosomal energy level, which in turn stimulates glycolysis; (b) glycolysis can be inhibited by higher concentrations of the radical; and (c) inhibitory effects on the energy-generating pathway and ATP level could contribute to NO toxicity under some in vivo situations.
研究了硝普钠和S-亚硝基半胱氨酸（两种能产生一氧化氮（NO）的化合物）对突触体能量产生途径和能量水平的影响。与硝普钠相比，S-亚硝基半胱氨酸使呼吸作用下降得更快且更显著。在完整的突触体中，10微摩尔的S-亚硝基半胱氨酸能抑制80%由葡萄糖和琥珀酸盐（加鱼藤酮）产生的呼吸作用，在破碎的制剂中能抑制80%由抗坏血酸盐/细胞色素c产生的呼吸作用。氧合血红蛋白能逆转和/或防止这种抑制作用，而谷胱甘肽（GSH）则会延长这种抑制作用。在有氧条件下，S-亚硝基半胱氨酸的存在会降低突触体的能量水平（磷酸肌酸/肌酸和ATP/ADP比值），而乳酸生成会增强。在孵育5分钟时对能量参数的影响大于15分钟时，且在GSH存在时更明显。在严格厌氧条件下，产生NO的化合物会以浓度依赖的方式降低乳酸生成。得出以下结论：（a）NO对氧化磷酸化的抑制导致突触体能量水平下降，进而刺激糖酵解；（b）更高浓度的该自由基可抑制糖酵解；（c）对能量产生途径和ATP水平的抑制作用可能在某些体内情况下导致NO毒性。
