Bioactivity-Guided Isolation of Neuritogenic Factor from the Seeds of the Gac Plant (Momordica cochinchinensis).
Bioactivity-Guided Isolation of Neuritogenic Factor from the Seeds of the Gac Plant (Momordica cochinchinensis).
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DOI：
10.1155/2018/8953958
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Soliman KFA
中科院分区：
文献类型：
--
作者：
Mazzio E;Badisa R;Eyunni S;Ablordeppey S;George B;Soliman KFA
神经生长因子（NGF）是一种内源性蛋白，具有诱导中枢神经系统（CNS）神经元分化和修复的功能。NGF信号包括其与原肌球蛋白相关激酶（Trk）受体的结合、内化和磷酸化级联反应的启动，磷酸化级联反应导致微管重组和神经元生长。由于神经生长因子不能穿过血脑屏障，其治疗用途受到限制。已知可以作为NGF受体激动剂（NGF模拟物）的合成肽可以减轻阿尔茨海默病和帕金森病实验模型中的神经退行性病理；然而，基于植物的NGF模拟物的存在是不确定的。因此，我们最近完成了超过1100种营养保健品（维生素，草药植物部分，多酚类物质，茶，水果和蔬菜）的高通量筛选，以使用PC-12细胞模型识别神经生成因子。值得注意的是，我们只发现了一种，通常被称为Gac植物（Momordica cochinchinensis） （MCS）的种子。在本研究中，我们利用生物活性引导化学分离进一步研究了该种子的神经生成作用。数据显示，在任何化学溶剂组分中都没有生物神经生成活性，活性仅为粗蛋白质所独有。然后通过1D电泳分离MSC粗蛋白，证实其具有活性的神经生成活性，分子量约为17 kDa。随后，17kDa波段被切除、消化，并在UPLC-MS/MS上运行，使用Q Exactive混合四极轨道rap质谱仪进行数据评估，如X！串联、OMS和K-score算法。17kDa带的蛋白质组学评估证实了11S球蛋白亚基β， napin, oleosin， Momordica胰蛋白酶抑制剂（TI） MCoTI-I /II和Two Inhibitor Peptide Topologies （TIPTOPs）的许多亚型的证据。虽然鉴定出的所有多肽都对应于Momordica cochinchinensis和Cucumis Sativus属/种，但该分析的一个重要限制是没有对Momordica cochinchinensis蛋白质组的完整注释。综上所述，这些发现表明MCS中存在一种质量为17kDa的稳定蛋白，具有诱导神经突生长的能力。未来的工作将需要建立MCS治疗神经退行性疾病的治疗价值。
Nerve growth factor (NGF) is an endogenously produced protein with the capacity to induce central nervous system (CNS) neuronal differentiation and repair. NGF signaling involves its binding to tropomyosin-related kinase (Trk) receptors, internalization, and initiation of phosphorylation cascades which cause microtubule reorganization and neuronal outgrowth. Because NGF cannot cross the blood-brain barrier, its therapeutic use is limited. Synthetic peptides that can act as NGF receptor agonists (NGF mimetics) are known to attenuate neurodegenerative pathologies in experimental models of Alzheimer's disease and Parkinson's disease; however, the existence of plant-based NGF mimetics is uncertain. For this reason, we recently completed a high throughput screening of over 1100 nutraceuticals (vitamins, herbal plant parts, polyphenolics, teas, fruits, and vegetables) to identify neuritogenic factor using a PC-12 cell model. Remarkably we found only one, commonly known as the seed of Gac plant (Momordica cochinchinensis) (MCS). In the current study, we further investigated this seed for its neuritogenic effect using bioactivity-guided chemical separations. The data show no biological neuritogenic activity in any chemical solvent fraction, where activity was exclusive to the crude protein. MSC crude proteins were then separated by 1D electrophoresis, where the active neuritogenic activity was confirmed to have a molecular mass of approximately 17 kDa. Subsequently, the 17kDa band was excised, digested, and run on a UPLC-MS/MS with a Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer with data evaluated diverse tools such as X! Tandem, OMS, and K-score algorithms. Proteomic evaluation of the 17kDa band confirmed evidence for 11S globulin subunit beta, napin, oleosin, Momordica trypsin inhibitors (TI) MCoTI-I /II, and many isoforms of Two Inhibitor Peptide Topologies (TIPTOPs). While all peptides identified correspond to the genus/species, Momordica cochinchinensis and Cucumis Sativus, a significant limitation of the analysis is the nonexistence of full annotation for the Momordica cochinchinensis proteome. In conclusion, these findings demonstrate that there is a stable protein within MCS having a mass of 17kDa with the capacity to induce neurite outgrowth. Future work will be required to establish the therapeutic value of the MCS for the treatment of neurodegenerative diseases.
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DOI：
10.3390/molecules21020152
发表时间：
2016-01-26
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Aboye T;Meeks CJ;Majumder S;Shekhtman A;Rodgers K;Camarero JA
通讯作者：
Camarero JA
影响因子：
4.6
作者：
Kolar MK;Itte VN;Kingham PJ;Novikov LN;Wiberg M;Kelk P
通讯作者：
Kelk P
影响因子：
2.9
作者：
Hernandez, JF;Gagnon, J;Nguyen, DL
通讯作者：
Nguyen, DL
影响因子：
4
作者：
Gao, Mingyong;Lu, Paul;Tuszynski, Mark
通讯作者：
Tuszynski, Mark
影响因子：
2.4
作者：
Betz, Volker M.;Sitoci-Ficici, K. Hakan;Kirsch, Matthias
通讯作者：
Kirsch, Matthias