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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Nitration of soluble proteins in organotypic culture models of Parkinson's disease.
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Nitration of soluble proteins in organotypic culture models of Parkinson's disease.

机译：帕金森病器官型培养模型中可溶性蛋白质的硝化。

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摘要

Protein nitration due to oxidative and nitrative stress has been linked to the pathogenesis of Parkinson's disease (PD), but its relationship to the loss of dopamine (DA) or tyrosine hydroxylase (TH) activity is not clear. Here we quantified protein-bound 3-nitrotyrosine (3-NT) by a novel gas chromatographyegative chemical ionization tandem mass spectrometry technique and DA and 3,4-dihydroxyphenylalanine (DOPA) by HPLC in tissues or medium of organotypic, mouse mesencephalon cultures after acute or chronic treatments with the peroxynitrite donor 3-morpholino-sydnonimine (SIN-1), the dopaminergic toxin 1-methyl-4-phenylpyridinium (MPP(+)) or the lipophilic complex I inhibitor rotenone. Incubation with SIN-1 (24 h) or MPP(+) treatments (48 h) caused dose-dependent protein nitration reaching a maximum of eightfold increase by 10 mM SIN-1 or twofold by 10 microM MPP(+), but significant DA depletions occurred at much lower concentrations of MPP(+) (1 microM). Chronic MPP(+) or rotenone treatments (3 weeks) caused maximum protein nitration by 1 microM (twofold) or 10nM (fourfold), respectively. Co-treatment with the nitric oxide synthase inhibitor l-NAME (300 microM) prevented protein nitration by MPP(+), but did not protect against MPP(+)-induced DA depletion or inhibition of TH activity. Acute incubation with 100 microM SIN-1 inhibited TH activity, which could be blocked by co-treatment with the tetrahydrobiopterin precursor l-sepiapterin, but tissue DA depletions required higher doses of SIN-1 (>1 mM, 24 h) and longer survival. In conclusion, protein nitration and TH activity or DA depletion are not directly related in these models.
机译：氧化和硝化应激导致的蛋白质硝化与帕金森氏病（PD）的发病机理有关，但尚不清楚其与多巴胺（DA）或酪氨酸羟化酶（TH）活性丧失的关系。在这里，我们通过一种新型的气相色谱/负化学电离串联质谱技术，通过HPLC在有机型，小鼠中脑培养的组织或培养基中定量测定了结合蛋白的3-硝基酪氨酸（3-NT），并通过HPLC定量了DA和3,4-二羟基苯丙氨酸（DOPA）。在使用过氧亚硝酸盐供体3-吗啉代亚砜（SIN-1），多巴胺能毒素1-甲基-4-苯基吡啶鎓（MPP（+））或亲脂性复合物I抑制剂鱼藤酮进行急性或慢性治疗后。与SIN-1（24 h）或MPP（+）处理（48 h）一起孵育会导致剂量依赖性蛋白质硝化作用，最大增加10 mM SIN-1增加8倍，或增加10 microM MPP（+）增加2倍，但DA显着增加耗尽发生在低得多的MPP（+）（1 microM）浓度下。慢性MPP（+）或鱼藤酮处理（3周）分别导致最大蛋白质硝化作用，分别为1 microM（两倍）或10nM（四倍）。与一氧化氮合酶抑制剂l-NAME（300 microM）的共同处理可防止MPP（+）引起的蛋白质硝化，但不能防止MPP（+）诱导的DA消耗或TH活性的抑制。与100 microM SIN-1的急性孵育抑制了TH活性，这可以通过与四氢生物蝶呤前体1-seaptapterin共同处理来阻断，但组织DA耗竭需要更高剂量的SIN-1（> 1 mM，24小时）和更长的生存期。总之，在这些模型中，蛋白质硝化作用和TH活性或DA耗竭并不直接相关。

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