Glutamate (GLT) is an essential neurotransmitter in the central nervous system. However, it has been emphasized that high GLT concentrations may play a critical role in the etiology of neurodegenerative diseases. One of the most essential damage mechanisms in neuronal cells induced by GLT is that it causes excessive Ca2+ entry into the cell, increasing intracellular oxidative stress. TRPM2 channel is a member of the TRP channel family, and its expression in neuronal cells is known. In addition, it is well known that the TRPM2 channel is activated by oxidative stress and is permeable to Ca2+. This study investigated the role of TRPM2 channel activation in the mechanism of GLT-induced excitotoxicity in SH‑SY5Y cells. Four groups were established for the study: control, 2-APB, GLT, and GLT+2-APB. SH‑SY5Y cells were pretreated with 2-APB (100 μM), a TRPM2 antagonist, 30 min before GLT (10 mM for 24 h) exposure. MTT assay was performed to determine cell viability. To determine TRPM2 channel activation in GLT excitotoxicity, ROS, PARP-1 and TRPM2 channel levels were determined in the cells. It was observed that exposure to high-dose GLT in cells increased the levels of ROS, PARP-1, and TRPM2 channels (p<0.05). In addition, ROS, PARP-1, and TRPM2 channel levels in the 2-APB pretreatment group (2-APB+GLT group) were found to be lower than the GLT group, with (p<0.05). In conclusion, it was determined that TRPM2 channel activation plays an essential role in the mechanism of GLT-induced excitotoxicity in neuronal cells. ORCID NO: 0000-0003-3637-7849
Anahtar Kelimeler: Glutamate, TRPM2, Oxidative Stress, PARP-1, SH‑SY5Y cells
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