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Upregulation of the nitrosylome in bipolar disorder type 1 (BP1) and major depression, but not BP2: Increased IgM antibodies to nitrosylated conjugates are associated with indicants of leaky gut.
Nitric Oxide ( IF 3.9 ) Pub Date : 2019-07-16 , DOI: 10.1016/j.niox.2019.07.003
Michael Maes 1 , Denitsa Simeonova 2 , Drozdstoy Stoyanov 2 , Jean-Claude Leunis 3
Affiliation  

OBJECTIVE Major depression (MDD) and a lifetime history of MDD are characterized by increased nitrosylation, while bipolar disorder type 1 (BP1), but not BP2, is accompanied by highly increased levels of oxidative stress and nitric oxide (NO) production. Nevertheless, it is unknown whether nitrosylation is involved in BP and whether there are differences in nitrosylation between BP1 and BP2. METHODS Serum IgM antibodies directed against nitroso (NO)-adducts were examined in MDD, BP1, BP2 and healthy controls, namely IgM responses to NO-cysteine, NO-tryptophan (NOW), NO-arginine and NO-albumin (SBA) in association with IgA/IgM responses to LPS of Gram-negative bacteria, IgG responses to oxidized low-density lipoprotein (ox-LDL) and serum peroxides. RESULTS Serum IgM levels against NO adducts were significantly higher in BP1 and MDD as compared with healthy controls, whereas BP2 patients occupied an intermediate position. IgM responses to NO-albumin were significantly higher in BP1 and MDD than in BP2 patients. There were highly significant associations between the IgM responses to NO-adducts and IgG responses to ox-LDL and IgA/IgM responses to Gram-negative bacteria. CONCLUSIONS BP1 and MDD are characterized by an upregulation of the nitrosylome (the proteome of nitrosylated proteins) and increased IgM responses to nitrosylated conjugates. Increased nitrosylation may be driven by increased bacterial translocation and is associated with lipid peroxidation processes. Innate-like (B1 and marginal zone) B cells and increased nitrosylation may play a key role in the major affective disorders through activation of immune-inflammatory and oxidative pathways, cardiovascular comorbidity and impairments in antioxidant defenses, neuro-glial interactions, synaptic plasticity, neuroprotection, neurogenesis.

中文翻译:

在双相情感障碍1型(BP1)和严重抑郁症中,但不是在BP2中,亚硝酰基组的上调:针对亚硝基化缀合物的IgM抗体增加与肠道渗漏的指标有关。

目的重度抑郁症(MDD)和MDD的终生史以亚硝化作用增强为特征,而双相情感障碍1型(BP1)而非BP2则伴随着氧化应激和一氧化氮(NO)产生的高度增加。然而,尚不清楚亚硝基化是否与BP有关,以及BP1和BP2之间的亚硝基化是否存在差异。方法在MDD,BP1,BP2和健康对照中检测针对亚硝基(NO)加合物的血清IgM抗体,即IgM对NO-半胱氨酸,NO-色氨酸(NOW),NO-精氨酸和NO-白蛋白(SBA)的反应。与IgA / IgM对革兰氏阴性菌LPS的反应,IgG对氧化的低密度脂蛋白(ox-LDL)和血清过氧化物的反应有关。结果与健康对照组相比,BP1和MDD中针对NO加合物的血清IgM水平明显高于健康对照组,而BP2患者处于中间位置。BP1和MDD患者对NO-白蛋白的IgM反应显着高于BP2患者。IgM对NO加合物的反应与IgG对ox-LDL的反应与IgA / IgM对革兰氏阴性菌的反应之间存在高度显着的关联。结论BP1和MDD的特征是亚硝酰基体(亚硝基化蛋白质的蛋白质组)上调,并且IgM对亚硝基化缀合物的反应增加。增加的亚硝基化可能由增加的细菌易位引起,并且与脂质过氧化过程有关。
更新日期:2019-11-01
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