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Transient Receptor Potential Melastatin 2 (TRPM2) Inhibition by Antioxidant, N -Acetyl-l-Cysteine, Reduces Global Cerebral Ischemia-Induced Neuronal Death.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Aug 21; Vol. 21 (17). Date of Electronic Publication: 2020 Aug 21. - Publication Year :
- 2020
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Abstract
- A variety of pathogenic mechanisms, such as cytoplasmic calcium/zinc influx, reactive oxygen species production, and ionic imbalance, have been suggested to play a role in cerebral ischemia induced neurodegeneration. During the ischemic state that occurs after stroke or heart attack, it is observed that vesicular zinc can be released into the synaptic cleft, and then translocated into the cytoplasm via various cation channels. Transient receptor potential melastatin 2 (TRPM2) is highly distributed in the central nervous system and has high sensitivity to oxidative damage. Several previous studies have shown that TRPM2 channel activation contributes to neuroinflammation and neurodegeneration cascades. Therefore, we examined whether anti-oxidant treatment, such as with N -acetyl-l-cysteine (NAC), provides neuroprotection via regulation of TRPM2, following global cerebral ischemia (GCI). Experimental animals were then immediately injected with NAC (150 mg/kg/day) for 3 and 7 days, before sacrifice. We demonstrated that NAC administration reduced activation of GCI-induced neuronal death cascades, such as lipid peroxidation, microglia and astroglia activation, free zinc accumulation, and TRPM2 over-activation. Therefore, modulation of the TRPM2 channel can be a potential therapeutic target to prevent ischemia-induced neuronal death.
- Subjects :
- Animals
Brain Ischemia metabolism
Brain Ischemia pathology
Glutathione metabolism
Hippocampus drug effects
Hippocampus metabolism
Hippocampus pathology
Lipid Peroxidation drug effects
Neuroglia drug effects
Neuroglia metabolism
Neuroglia pathology
Neurons metabolism
Neurons pathology
Rats
TRPM Cation Channels antagonists & inhibitors
Zinc metabolism
Acetylcysteine pharmacology
Antioxidants pharmacology
Brain Ischemia drug therapy
Neurons drug effects
TRPM Cation Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32825703
- Full Text :
- https://doi.org/10.3390/ijms21176026