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Magnesium-Induced Cell Survival Is Dependent on TRPM7 Expression and Function
Yuyang Sun1, Pramod Sukumaran1, Brij B Singh2
1Department of Periodontics, School of Dentistry, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
Molecular Neurobiology
|August 9, 2019
Summary
Transient receptor potential melastatin 7 (TRPM7) regulates magnesium (Mg2+) homeostasis in dopaminergic cells. TRPM7 channels are crucial for preventing neurotoxin-induced cell death and maintaining neuronal survival.
Area of Science:
- Neuroscience
- Cell Biology
- Ion Channel Physiology
Background:
- Magnesium (Mg2+) homeostasis is vital for cell survival, and its dysregulation is linked to neurodegenerative diseases like Parkinson's.
- The specific ion channels controlling Mg2+ levels in dopaminergic neurons and protecting against neurotoxins remain unidentified.
Purpose of the Study:
- To investigate the role of TRPM7 (transient receptor potential melastatin 7) in regulating Mg2+ homeostasis in dopaminergic cells.
- To determine if TRPM7 is involved in the survival of dopaminergic neurons under neurotoxic conditions.
Main Methods:
- Utilized dopaminergic SH-SY5Y cells and mouse substantia nigra pars compacta.
- Assessed intracellular Mg2+ levels, cell survival, caspase-3 activity, and mitochondrial membrane potential.
- Manipulated TRPM7 expression (silencing and overexpression) and Mg2+ levels.
Main Results:
- Transient loss of TRPM7 reduced intracellular Mg2+ and dopaminergic cell survival.
- Increased extracellular Mg2+ or TRPM7 levels protected cells against neurotoxins.
- Neurotoxin treatment decreased TRPM7 levels and Mg2+ influx.
- Mg2+ supplementation enhanced survival, restored mitochondrial function, and increased TRPM7 levels, effects dependent on TRPM7 presence.
Conclusions:
- TRPM7 channels play a significant role in maintaining Mg2+ homeostasis in dopaminergic cells.
- TRPM7 is critical for protecting dopaminergic neurons against neurotoxin-induced cell death.
- Targeting TRPM7 and Mg2+ homeostasis offers a potential therapeutic strategy for neurodegenerative diseases.
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