ABSTRACT

Transient Receptor Potential Melastatin-like 7 (TRPM7), Transient Receptor Potential Melastatin-like 8 (TRPM8) and Transient Receptor Potential Vanilloid-like 1 (TRPV1) channels are expressed in neurological tissues such as brain cortex, dorsal root ganglion and hippocampal neurons and involved in several neurological diseases. The SH-SY5Y neuronal cell line is frequently used as a cellular model of neurodegenerative diseases including Parkinson’s disease. The differentiated SH-SY5Y cells have much neuronal structure, function and exaggerated neuronal marker expression. However, we have less data about how differentiation induces TRP channel expression and how TRP channels have a role in cellular functions in Parkinson’s disease model in SH-SY5Y cells. Hence, we aimed to investigate the effects of differentiation phenomena on TRPM7, TRPM8 and TRPV1 cation channel expression and related Ca²⁺ signaling. We also made some other analysis to elucidate TRP channels’ function in MPP induced apoptosis, mitochondrial membrane potential levels, intracellular reactive oxygen species production, caspase 3 and caspase 9 enzyme activities in differentiated or undifferentiated SH-SY5Y neuronal cells. Herein we concluded that TRPM7, TRPM8 and TRPV1 cation channels have pivotal effects on differentiation and MPP induced Parkinson’s disease model in SH-SY5Y cells.

摘要

瞬时受体电位 Melastatin-like 7 (TRPM7)、瞬时受体电位 Melastatin-like 8 (TRPM8) 和瞬时受体电位 Vanilloid-like 1 (TRPV1) 通道在脑皮层、背根神经节和海马神经元等神经组织中表达，涉及多种神经系统疾病。SH-SY5Y 神经元细胞系经常用作包括帕金森病在内的神经退行性疾病的细胞模型。分化的SH-SY5Y细胞具有大量的神经元结构、功能和夸张的神经元标志物表达。然而，关于分化如何诱导 TRP 通道表达以及 TRP 通道如何在 SH-SY5Y 细胞中帕金森病模型的细胞功能中发挥作用的数据较少。因此，我们旨在研究分化现象对 TRPM7 的影响，²⁺信号。我们还进行了一些其他分析，以阐明 TRP 通道在 MPP 诱导的细胞凋亡中的功能、线粒体膜电位水平、细胞内活性氧物质的产生、分化或未分化的 SH-SY5Y 神经元细胞中的半胱天冬酶 3 和半胱天冬酶 9 酶活性。在此我们得出结论，TRPM7、TRPM8 和 TRPV1 阳离子通道对 SH-SY5Y 细胞的分化和 MPP 诱导的帕金森病模型具有关键作用。