MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Cell Signal. 2017 Sep;37:103-114. doi: 10.1016/j.cellsig.2017.06.007. Epub 2017 Jun 13.
The vesicular monoamine transporter 2 (VMAT2) pumps dopamine from cytoplasm into synaptic vesicles for subsequent release, and the deficits of VMAT2 has been implicated in the dopaminergic neuronal cell loss which is considered as a typical pathological feature of Parkinson's disease (PD). Low-power laser irradiation (LPLI), a potent noninvasive physiotherapy approach, is capable of penetrating into nerve tissue to exert beneficial effects such as promoting nerve regeneration and ATP production. In the present study, we demonstrated that LPLI protects against MPP-induced neurotoxicity via upregulation of VMAT2 in SH-SY5Y human dopaminergic neuroblastoma cells. The photoactivation of ERK phosphorylated cAMP-response element binding protein (CREB) at Ser133, and thus increased the ability of CREB binding to the promoter region of VMAT2, leading to elevated VMAT2 expression, which contributes to dopamine release and cell survival. Taken together, for the first time to our knowledge, the results showed that LPLI attenuates MPP-induced neurotoxicity through activation of ERK/CREB/VMAT2 pathway, suggesting that the manipulation of VMAT2 by LPLI may provide a potential therapeutic strategy for PD.
囊泡单胺转运体 2（VMAT2）将多巴胺从细胞质泵入突触小泡以备随后释放，VMAT2 的缺陷与多巴胺能神经元细胞丢失有关，后者被认为是帕金森病（PD）的典型病理特征。低强度激光辐射（LPLI）是一种强大的无创物理治疗方法，能够穿透神经组织发挥有益作用，如促进神经再生和 ATP 产生。在本研究中，我们证明 LPLI 通过上调 SH-SY5Y 人多巴胺能神经母细胞瘤细胞中的 VMAT2 来防止 MPP 诱导的神经毒性。ERK 磷酸化 cAMP 反应元件结合蛋白（CREB）在 Ser133 的光激活，从而增加了 CREB 与 VMAT2 启动子区域结合的能力，导致 VMAT2 表达升高，从而促进多巴胺释放和细胞存活。总之，据我们所知，这是首次表明 LPLI 通过激活 ERK/CREB/VMAT2 途径来减轻 MPP 诱导的神经毒性，这表明 LPLI 对 VMAT2 的操纵可能为 PD 提供一种潜在的治疗策略。
