Magnesium-Induced Cell Survival Is Dependent on TRPM7 Expression and Function

Mg 2+ homeostasis is essential for cell survival and the loss of this regulation has been associated with many neurodegenerative diseases, including loss of dopaminergic neurons. Although the neurotoxin-mediated loss of dopaminergic neurons in Parkinson disease models is extensively studied, the ion...

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Bibliographic Details
Published in:Molecular neurobiology 2020-01, Vol.57 (1), p.528-538
Main Authors: Sun, Yuyang, Sukumaran, Pramod, Singh, Brij B.
Format: Article
Language:English
Subjects:
Apoptosis
Biomedical and Life Sciences
Biomedicine
Caspase
Caspase-3
Cell Biology
Cell death
Cell survival
Dopamine receptors
Homeostasis
Magnesium
Membrane potential
Mitochondria
Movement disorders
Neurobiology
Neurodegenerative diseases
Neurology
Neurosciences
Neurotoxins
Parkinson's disease
Substantia nigra
Supplements
Survival
Transient receptor potential proteins
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Summary:Mg 2+ homeostasis is essential for cell survival and the loss of this regulation has been associated with many neurodegenerative diseases, including loss of dopaminergic neurons. Although the neurotoxin-mediated loss of dopaminergic neurons in Parkinson disease models is extensively studied, the ion channel(s) that regulate Mg 2+ homeostasis and thus could prevent neuronal cell death is not yet identified. Here, we show that TRPM7 (transient receptor potential melastatin 7) is involved in regulating Mg 2+ homeostasis in dopaminergic cells. Importantly, transient loss of TRPM7 decreased intracellular Mg 2+ levels and decreased dopaminergic cells/neurons survival. We provide further evidence that both increases in extracellular Mg 2+ or transiently increasing TRPM7 levels protected dopaminergic SH-SY5Y cells against neurotoxin-mediated cell death. Neurotoxin treatment significantly decreased TRPM7 levels in both SH-SY5Y cells and the substantia nigra pars compacta region of mice, along with a decrease in Mg 2+ influx. Moreover, Mg 2+ supplementation showed a concentration-dependent decrease in caspase-3 activity, an increase in cell survival, restored mitochondrial membrane potential, and increase TRPM7 levels in neurotoxin-treated cells. In contrast, transient silencing of TRPM7 inhibited the positive effect of Mg 2+ supplementation in protecting against neurotoxins. Whereas, TRPM7 overexpression not only maintained Mg 2+ homeostasis but also inhibited caspase 3 activity that induced cell survival. Overall, these results suggest a significant role of TRPM7 channels in Mg 2+ homeostasis and the survival of neurotoxin-induced loss of dopaminergic cells.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-019-01713-7