Protective role of selenium on MPP⁺ and homocysteine-induced TRPM2 channel activation in SH-SY5Y cells

Abstract

Homocysteine is an intermediate product of biochemical reactions occurring in living organisms. It is known that drugs that increase dopamine synthesis used in Parkinson's disease (PD) cause an increase in the plasma homocysteine level. As the plasma homocysteine level increases, the amount of intracellular free calcium ion ([Ca²⁺]_i) and oxidative stress increase. As a result, it contributes to the excitotoxic effect by causing neurodegeneration. TRPM2 cation channel is activated by high [Ca²⁺]_i and oxidative stress. The role of TRPM2 in the development of neuronal damage due to the increase in homocysteine in PD has not yet been elucidated. In current study, we aimed to investigate the role of the TRPM2 and selenium (Se) in SH-SY5Y neuronal cells treated with homocysteine (HCT) and MPP . SH-SY5Y cells were divided into four groups: control, MPP, MPP + HCT, and MPP + HCT + Se. The results of plate reader assay, confocal microscope imaging, and western blot analyses indicated upregulation of apoptosis, [Ca²⁺]_i, mitochondrial membrane depolarization, caspase activation, and intracellular ROS values in the cells. The MPP + HCT group had considerably higher values than the other groups. The MPP + HCT + Se group had significantly lower values than all the other groups except the control group. In addition, incubation of MPP + HCT and MPP + HCT + Se groups with TRPM2 antagonist 2-APB increased cell viability and reduced intracellular calcium influx and apoptosis levels. It is concluded that the activation of TRPM2 was propagated in HCT and MPP-induced SH-SY5Y cells by the increase of oxidative stress. The antioxidant property of Se regulated the TRPM2 channel activation and neurodegeneration by providing intracellular oxidant/antioxidant balance.

Keywords:

• Parkinson's disease
• MPP⁺
• homocysteine
• SH-SY5Y cell
• TRPM2
• selenium

Acknowledgements

The results of this study were presented as posters at 31st National Biophysics Congress, 09 October 2019, Adana, Turkey by KY and MN. https://www.turkbiyofizikdernegi.org/kongre2019.html

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This study was carried out with a financial support from BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry Ltd. Inc. (Göller Bölgesi Teknokenti, Isparta, Turkey) [Project No: 2019-20].