Proteomic characterization of secretory granules in dopaminergic neurons indicates chromogranin/secretogranin-mediated protein processing impairment in Parkinson's disease.
Proteomic characterization of secretory granules in dopaminergic neurons indicates chromogranin/secretogranin-mediated protein processing impairment in Parkinson's disease.
复制标题
多巴胺能神经元分泌颗粒的蛋白质组学特征表明帕金森病中嗜铬粒蛋白/分泌粒蛋白介导的蛋白质加工受损
DOI：
10.18632/aging.203415
复制
发表时间：
2021-08-21
期刊：
影响因子：
--
通讯作者：
Zhan X
中科院分区：
文献类型：
--
作者：
Wen G;Pang H;Wu X;Jiang E;Zhang X;Zhan X
帕金森病(PD)是一种与囊泡运输功能障碍和神经递质分泌有关的衰老障碍。分泌颗粒(SGS)是一种大而致密的囊泡，用于神经肽和激素的生物合成。目前，SGS损伤在帕金森病中的作用尚不清楚。在本研究中，我们发现1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)染毒小鼠黑质和纹状体中酪氨酸羟基酶阳性神经元的SGS数量和标记蛋白分泌性颗粒素III(Scg3)显著减少。对1-甲基-4-苯基吡啶(MPP+)处理的多巴胺能SH-SY5Y细胞(ProteomeXchange PXD023937)纯化的SGS进行蛋白质组学研究，鉴定出536个显著差异表达的蛋白质。结果表明，溶酶体和过氧化物体功能障碍、脂代谢紊乱和能量代谢紊乱是本病的三大特征。对56个分泌蛋白和140个分泌蛋白的蛋白质-蛋白质相互作用分析表明，SGS中嗜铬粒/分泌颗粒介导的多肽加工明显受损，伴随着候选蛋白质和多肽神经分泌蛋白(VGF)、神经肽Y、载脂蛋白E的减少和前脑啡肽水平的增加。目前的研究提供了广泛的帕金森病患者的SGS蛋白图谱。这有助于了解该病的分子机制。
Parkinson’s disease (PD) is an aging disorder related to vesicle transport dysfunctions and neurotransmitter secretion. Secretory granules (SGs) are large dense-core vesicles for the biosynthesis of neuropeptides and hormones. At present, the involvement of SGs impairment in PD remains unclear. In the current study, we found that the number of SGs in tyrosine hydroxylase-positive neurons and the marker proteins secretogranin III (Scg3) significantly decreased in the substantia nigra and striatum regions of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) exposed mice. Proteomic study of SGs purified from the dopaminergic SH-sy5Y cells under 1-methyl-4-phenylpyridinium (MPP+) treatments (ProteomeXchange PXD023937) identified 536 significantly differentially expressed proteins. The result indicated that disabled lysosome and peroxisome, lipid and energy metabolism disorders are three characteristic features. Protein-protein interaction analysis of 56 secretory proteins and 140 secreted proteins suggested that the peptide processing mediated by chromogranin/secretogranin in SGs was remarkably compromised, accompanied by decreased candidate proteins and peptides neurosecretory protein (VGF), neuropeptide Y, apolipoprotein E, and an increased level of proenkephalin. The current study provided an extensive proteinogram of SGs in PD. It is helpful to understand the molecular mechanisms in the disease.
DOI：
10.1111/apha.13046
发表时间：
2018-06
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Stenovec M;Trkov Bobnar S;Smolič T;Kreft M;Parpura V;Zorec R
通讯作者：
Zorec R