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下调 TRPM7、TRPM8 和 TRPV1 通道可调节细胞凋亡参数和神经退行性标记物:聚焦于神经元分化和帕金森病模型。

Downregulation of TRPM7, TRPM8, and TRPV1 channels modulate apoptotic parameters and neurodegenerative markers: Focus on neuronal differentiation and Parkinson's disease model.

机构信息

Department of Biophysics, School of Medicine, Süleyman Demirel University, Isparta, Turkey.

Neuroscience Research Center, Süleyman Demirel University, Isparta, Turkey.

出版信息

Cell Biol Int. 2023 Sep;47(9):1502-1518. doi: 10.1002/cbin.12048. Epub 2023 May 19.

DOI:10.1002/cbin.12048
PMID:37208975
Abstract

The transient receptor potential channel (TRP) channels are expressed in neuronal tissues and involved in neurological diseases such as pain, epilepsy, neuronal apoptosis, and neurodegenerative diseases. Formerly, we have investigated how neuronal differentiation changes TRP channels expression profile and how Parkinson's disease model is related with this expression levels. We have found that transient receptor potential channel melastatin subtype 7 (TRPM7), transient receptor potential channel melastatin subtype 8 and transient receptor potential channel vanilloid subtype 1 (TRPV1) channels have pivotal effects on differentiation and 1-Methyl-4-phenylpyridinium (MPP )-induced Parkinson's disease model in SH-SY5Y cells. In this study, we have investigated that downregulation of the TRP channels to evaluate how differentiation status changes to Parkinson's disease pathological hallmarks. We have also performed to other analyses to elucidate these TRP channels' function in MPP -induced neurotoxicity related apoptosis, cell viability, caspase 3 and 9 enzyme activities, intracellular reactive oxygen species production, mitochondrial depolarization levels, Ca signaling, Alpha-synuclein and Dopamine levels, mono amino oxidase A and B enzymatic activities, both in differentiated and undifferentiated neuronal cells. Herein we have concluded that especially TRPM7 and TRPV1 channels have distinct role in Parkinson's disease pathology via their activity changings in pathological state, and downregulation of these channels or specific antagonists can be useful for the possible treatment strategy for Parkinson's disease and related markers.

摘要

瞬时受体电位通道 (TRP) 通道在神经组织中表达,参与疼痛、癫痫、神经元凋亡和神经退行性疾病等神经系统疾病。以前,我们研究了神经元分化如何改变 TRP 通道的表达谱,以及帕金森病模型与这些表达水平的关系。我们发现瞬时受体电位通道 melastatin 亚家族 7 (TRPM7)、瞬时受体电位通道 melastatin 亚家族 8 和瞬时受体电位通道香草素亚型 1 (TRPV1) 通道对分化和 1-甲基-4-苯基吡啶离子 (MPP)诱导的 SH-SY5Y 细胞帕金森病模型具有重要作用。在这项研究中,我们研究了 TRP 通道的下调,以评估分化状态如何改变帕金森病的病理特征。我们还进行了其他分析,以阐明这些 TRP 通道在 MPP 诱导的神经毒性相关凋亡、细胞活力、半胱天冬酶 3 和 9 酶活性、细胞内活性氧产生、线粒体去极化水平、Ca 信号、α-突触核蛋白和多巴胺水平、单胺氧化酶 A 和 B 酶活性中的作用,在分化和未分化的神经元细胞中。在此,我们得出结论,特别是 TRPM7 和 TRPV1 通道通过其在病理状态下的活性变化在帕金森病病理中具有独特的作用,下调这些通道或特异性拮抗剂可能对帕金森病和相关标志物的可能治疗策略有用。

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