System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India.
Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India.
Mol Neurobiol. 2018 Nov;55(11):8278-8292. doi: 10.1007/s12035-018-0986-z. Epub 2018 Mar 10.
The role of resveratrol (RV) as a neuroprotectant is well recognized, and cellular molecules involved in imparting the physiological effect have been well illustrated. However, some ambiguity still prevails as the specific receptor, and downstream signaling molecules are not yet clearly stated. So, we investigated the signaling pathway(s) involved in its cellular protection in the human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived neuronal cells. The mesenchymal stem cells were exposed to various concentrations (10, 100, 1000 μM) of monocrotophos (MCP), a known developmental neurotoxic organophosphate pesticide, for a period of 24 h. The MAPK signaling pathways (JNK, p38, and ERK) known to be associated with MCP-induced damages were also taken into consideration to identify the potential connection. The biological safe dose of RV (10 μM) shows a significant restoration in the MCP-induced alterations. Under the specific growth conditions, RV exposure was found to promote neuronal differentiation in the hUCB-MSCs. The exposure of cells to a specific pharmacological inhibitor (LY294002) of PI3K confirms the significant involvement of PI3K-mediated pathway in the ameliorative responses of RV against MCP exposure. Our data identifies the substantial role of RV in the restoration of MCP-induced cellular damages, thus proving to have a therapeutic potential against organophosphate pesticide-induced neurodegeneration.
白藜芦醇(RV)作为神经保护剂的作用已得到广泛认可,赋予其生理效应的细胞分子也已得到充分阐明。然而,由于特定的受体和下游信号分子尚不清楚,仍存在一些模糊性。因此,我们研究了其在人脐带来源间充质干细胞(hUCB-MSC)衍生神经元细胞中的细胞保护所涉及的信号通路。将间充质干细胞暴露于不同浓度(10、100、1000μM)的久效磷(MCP)中,MCP 是一种已知的发育神经毒性有机磷农药,暴露时间为 24 小时。还考虑了与 MCP 诱导损伤相关的 MAPK 信号通路(JNK、p38 和 ERK),以确定潜在的联系。RV 的生物安全剂量(10μM)显示出对 MCP 诱导的变化的显著恢复。在特定的生长条件下,RV 暴露被发现可促进 hUCB-MSCs 中的神经元分化。细胞暴露于特定的 PI3K 药理学抑制剂(LY294002)证实了 PI3K 介导的途径在 RV 对 MCP 暴露的改善反应中的重要参与。我们的数据确定了 RV 在恢复 MCP 诱导的细胞损伤方面的重要作用,从而证明其对有机磷农药诱导的神经退行性变具有治疗潜力。