Department of Medicine, University of California Medical Center, San Francisco, CA, USA.
Campus for Jewish Living, San Francisco, CA, USA.
FASEB J. 2021 Feb;35(2):e21339. doi: 10.1096/fj.202002519R.
Neuroprotective and other functional proteins of mitochondria were quantified in extracts of plasma neural-derived exosomes from ten first-episode psychosis (FP) patients and ten matched psychiatrically normal controls (ctls). Astrocyte-derived extracellular vesicles (ADEVs) and neuron-derived extracellular vesicles (NDEVs) were immunoabsorbed separately from physically precipitated plasma total EVs. Extracted mitochondrial ATP synthase was specifically immunofixed to plastic wells for quantification of catalytic activity based on conversion of NADH to NAD . Other extracted mitochondrial functional proteins were quantified by ELISAs. All protein levels were normalized with EV content of the CD81 exosome marker. FP patient ADEV level but not NDEV level of mitochondrial ATP synthase activity was significantly lower than that of ctls. FP patient ADEV and NDEV levels of the functionally critical mitochondrial proteins mitofusin 2 and cyclophilin D, but not of transcription factor A of mitochondria, and of the mitochondrial short open-reading frame neuroprotective and metabolic regulatory peptides humanin and MOTS-c were significantly lower than those of ctls. In contrast, FP patient NDEV, but not ADEV, level of the mitochondrial-tethering protein syntaphilin, but not of myosin VI, was significantly higher than that of ctls. The distinctively different neural levels of some mitochondrial proteins in FP patients than ctls now should be correlated with diverse clinical characteristics. Drugs that increase depressed levels of proteins and mimetics of deficient short open-reading frame peptides may be of therapeutic value in early phases of schizophrenia.
从十个首发精神病（FP）患者和十个匹配的精神病正常对照（CTL）的血浆神经源性外泌体提取物中定量了神经保护和其他功能蛋白。分别从物理沉淀的血浆总 EV 中免疫吸收星形胶质细胞衍生的细胞外囊泡（ADEV）和神经元衍生的细胞外囊泡（NDEV）。提取的线粒体 ATP 合酶特异性免疫固定在塑料孔中，根据 NADH 向 NAD 的转化来定量催化活性。其他提取的线粒体功能蛋白通过 ELISA 定量。所有蛋白质水平均与 CD81 外泌体标志物的 EV 含量进行归一化。FP 患者 ADEV 水平而非 NDEV 水平的线粒体 ATP 合酶活性明显低于 CTL。FP 患者 ADEV 和 NDEV 水平的功能关键线粒体蛋白融合蛋白 2 和细胞色素 P450 D，而不是线粒体转录因子 A，以及线粒体短开放阅读框神经保护和代谢调节肽人源和 MOTS-c 的水平明显低于 CTL。相比之下，FP 患者 NDEV 水平而非 ADEV 水平的线粒体连接蛋白 syntaphilin 明显高于 CTL，但肌球蛋白 VI 则不然。FP 患者与 CTL 相比，某些线粒体蛋白在神经水平上的明显不同，现在应该与不同的临床特征相关。增加蛋白质和缺乏短开放阅读框肽模拟物的药物在精神分裂症的早期阶段可能具有治疗价值。
