scholarly journals Effects of transient receptor potential cation channel 5 (TRPC5) inhibition on global cerebral ischemia-induced neuronal death

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S219-S220
Author(s):  
Beom Seok Kang ◽  
Bo Young Choi ◽  
A Ra Kho ◽  
Song Hee Lee ◽  
Dae Ki Hong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Global Cerebral Ischemia ◽  
Transient Receptor

scholarly journals Carvacrol Attenuates Hippocampal Neuronal Death after Global Cerebral Ischemia via Inhibition of Transient Receptor Potential Melastatin 7

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 231 ◽  
Author(s):  
Dae Hong ◽  
Bo Choi ◽  
A Kho ◽  
Song Lee ◽  
Jeong Jeong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Receptor Potential ◽  
Global Cerebral Ischemia ◽  
Neuroprotective Effects ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Zinc Translocation

Over the last two decades, evidence supporting the concept of zinc-induced neuronal death has been introduced, and several intervention strategies have been investigated. Vesicular zinc is released into the synaptic cleft, where it then translocates to the cytoplasm, which leads to the production of reactive oxygen species and neurodegeneration. Carvacrol inhibits transient receptor potential melastatin 7 (TRPM7), which regulates the homeostasis of extracellular metal ions, such as calcium and zinc. In the present study, we test whether carvacrol displays any neuroprotective effects after global cerebral ischemia (GCI), via a blockade of zinc influx. To test our hypothesis, we used eight-week-old male Sprague–Dawley rats, and a GCI model was induced by bilateral common carotid artery occlusion (CCAO), accompanied by blood withdrawal from the femoral artery. Ischemic duration was defined as a seven-minute electroencephalographic (EEG) isoelectric period. Carvacrol (50 mg/kg) was injected into the intraperitoneal space once per day for three days after the onset of GCI. The present study found that administration of carvacrol significantly decreased the number of degenerating neurons, microglial activation, oxidative damage, and zinc translocation after GCI, via downregulation of TRPM7 channels. These findings suggest that carvacrol, a TRPM7 inhibitor, may have therapeutic potential after GCI by reducing intracellular zinc translocation.

scholarly journals Transient Receptor Potential Melastatin 2 (TRPM2) Inhibition by Antioxidant, N-Acetyl-l-Cysteine, Reduces Global Cerebral Ischemia-Induced Neuronal Death

2020 ◽  
Vol 21 (17) ◽  
pp. 6026 ◽  
Author(s):  
Dae Ki Hong ◽  
A Ra Kho ◽  
Song Hee Lee ◽  
Jeong Hyun Jeong ◽  
Beom Seok Kang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Sensitivity ◽  
Synaptic Cleft ◽  
Global Cerebral Ischemia ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channel ◽  
Transient Receptor

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.

scholarly journals Functional Restoration following Global Cerebral Ischemia in Juvenile Mice following Inhibition of Transient Receptor Potential M2 (TRPM2) Ion Channels

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Robert M. Dietz ◽  
James E. Orfila ◽  
Nicholas Chalmers ◽  
Crystal Minjarez ◽  
Jose Vigil ◽  
...  
Keyword(s):  
Cell Death ◽  
Ion Channels ◽  
Cerebral Ischemia ◽  
Transient Receptor Potential ◽  
Memory Function ◽  
Receptor Potential ◽  
Functional Restoration ◽  
Global Cerebral Ischemia ◽  
Trpm2 Channels ◽  
Transient Receptor

Hippocampal cell death and cognitive dysfunction are common following global cerebral ischemia across all ages, including children. Most research has focused on preventing neuronal death. Restoration of neuronal function after cell death is an alternative approach (neurorestoration). We previously identified transient receptor potential M2 (TRPM2) ion channels as a potential target for acute neuroprotection and delayed neurorestoration in an adult CA/CPR mouse model. Cardiac arrest/cardiopulmonary resuscitation (CA/CPR) in juvenile (p20-25) mice was used to investigate the role of ion TRPM2 channels in neuroprotection and ischemia-induced synaptic dysfunction in the developing brain. Our novel TRPM2 inhibitor, tatM2NX, did not confer protection against CA1 pyramidal cell death but attenuated synaptic plasticity (long-term plasticity (LTP)) deficits in both sexes. Further, in vivo administration of tatM2NX two weeks after CA/CPR reduced LTP impairments and restored memory function. These data provide evidence that pharmacological synaptic restoration of the surviving hippocampal network can occur independent of neuroprotection via inhibition of TRPM2 channels, providing a novel strategy to improve cognitive recovery in children following cerebral ischemia. Importantly, these data underscore the importance of age-appropriate models in disease research.

scholarly journals Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 397
Author(s):  
Andras Szollosi
Keyword(s):  
Structure Function ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Immune Cell ◽  
Receptor Potential ◽  
Cation Channel ◽  
Biophysical Properties ◽  
Vast Number ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The transient receptor potential melastatin (TRPM) family belongs to the superfamily of TRP ion channels. It consists of eight family members that are involved in a plethora of cellular functions. TRPM2 is a homotetrameric Ca2+-permeable cation channel activated upon oxidative stress and is important, among others, for body heat control, immune cell activation and insulin secretion. Invertebrate TRPM2 proteins are channel enzymes; they hydrolyze the activating ligand, ADP-ribose, which is likely important for functional regulation. Since its cloning in 1998, the understanding of the biophysical properties of the channel has greatly advanced due to a vast number of structure–function studies. The physiological regulators of the channel have been identified and characterized in cell-free systems. In the wake of the recent structural biochemistry revolution, several TRPM2 cryo-EM structures have been published. These structures have helped to understand the general features of the channel, but at the same time have revealed unexplained mechanistic differences among channel orthologues. The present review aims at depicting the major research lines in TRPM2 structure-function. It discusses biophysical properties of the pore and the mode of action of direct channel effectors, and interprets these functional properties on the basis of recent three-dimensional structural models.

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