도파민성 뉴런 사멸의 파킨슨병 발병에 TRPC5 이온통로의 산화적 활성 억제 효과 연구

Abstract

Parkinson's disease is known as a typical senile disease such as dementia and stroke. Parkinson's disease is caused by a decrease in dopamine secretion due to the death of dopamineergic neuron located in substantia nigra, which produces dopamine. Oxidative stress is known to be the cause of the death of dopaminergic neuron. Rotenone, which is mainly used in the study of Parkinson's disease, is a mitochondrial complex 1 inhibitor that induces oxidative stress caused by mitochondrial damage. Diamide reduces the reduction of reactive oxygen species (ROS) by changing the reduced glutathione (GSH), an intracellular reducing agent, to oxidized glutathione (GSSG), and induces oxidative stress to induce cell death. Oxidative stress is the main cause of Parkinson's disease, but the mechanisms for inducing oxidative stress by patient are not the same. To identify differences between oxidative stress-induced mechanisms, we compared rotenone and diamide with different oxidative stress-induced mechanisms. Mitochondrial membrane potential, active oxygen, and cell death were compared using SH-SY5Y cells, a neurogenic cell species. After treating SH-SY5Y cells with fluorescent dye, the intracellular signal change was measured through live cell imaging. Rotenone induced hyperpolarization of mitochondrial membrane potential from the early stage by direct inhibition of mitochondrial complex 1, and by blocking oxidative phosphorylation of mitochondria, an increase in ROS induced oxidative stress and induced cell death. Diamide did not affect mitochondria, and reduction of ROS through GSH reduction, an intracellular reducing agent, induced oxidative stress and induced cell death. A Transient Receiver Potential Channel canonical type 5 (TRPC5) which is a Ca2+- permeable non-selective cation channel is activated by intracellular oxidation. The effect of blocking the TRPC5 ion channel by the intracellular oxidative stress induction mechanism was compared. In treating the TRPC5 ion channel blocker Pico145, there is no difference in cell death by rotenone, but cell death by diamide was reduced.