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

Transient receptor potential melastatin 2 channels in neurological disorders: Mechanisms and animal models

“…This is replicated in SH-SY5Y cells exposed to MPP + and homocysteine, which display high levels of ROS, mitochondrial membrane depolarization, and activation of caspases (enzymes involved in apoptosis) [47] . This effect was reduced by selenium, an antioxidant, and 2-APB, a TRPM2 inhibitor, which decrease apoptosis and Ca 2+ influx [47] . In SH-SY5Y cells overexpressing TRPM2, cell viability was reduced relative to wild-type cells in response to H 2 O 2 exposure, which was prevented by TRPM2 and PARP inhibition [48] .…”

“…In addition, they possess catecholaminergic properties, such as the ability to produce dopamine [46] . In PD patients administered with dopamine synthesisenhancing drugs, homocysteine is produced as a byproduct, which may cause side effects, such as apoptosis and oxidative stress, contributing to PD development [47] . This is replicated in SH-SY5Y cells exposed to MPP + and homocysteine, which display high levels of ROS, mitochondrial membrane depolarization, and activation of caspases (enzymes involved in apoptosis) [47] .…”

“…In PD patients administered with dopamine synthesisenhancing drugs, homocysteine is produced as a byproduct, which may cause side effects, such as apoptosis and oxidative stress, contributing to PD development [47] . This is replicated in SH-SY5Y cells exposed to MPP + and homocysteine, which display high levels of ROS, mitochondrial membrane depolarization, and activation of caspases (enzymes involved in apoptosis) [47] . This effect was reduced by selenium, an antioxidant, and 2-APB, a TRPM2 inhibitor, which decrease apoptosis and Ca 2+ influx [47] .…”

“…Parkinson's disease 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine Increased TRPM2 expression in substantia nigra; TRPM2 and PARP inhibition improve cognition and locomotion [38,43] 6-hydroxydopamine Upregulation of TRPM2 in substantia nigra [44] Rotenone (insecticide) Exposure Induced TRPM2-mediated currents [45] MPP + and homocysteine exposure in SH-SY5Y cells TRPM2 inhibition with antioxidant, selenium, reduced apoptosis, and Ca 2+ -influx [47] MPP + exposure in SH-SY5Y cells Increased TRPM2 expression associated with increased caspase activation and reduced cell viability [48][49][50] Alzheimer's disease APP/PS1 TRPM2 -/-APP/PS1 mice possessed decreased ER stress and reduced synaptic loss [61] TRPM2 -/-TRPM2 -/mice exhibit decrease microglia activation; TRPM2 -/microglial cells are not activated and do not generate TNF-α in response to Aβ [61,62] Aβ and H 2 O 2 exposure in rat striatal cells TRPM2 downregulation inhibits the elevation of intracellular calcium levels and cell death [59] Aβ exposure in hippocampal neurons Increased TRPM2-mediated currents [61] Ischemic stroke Transient middle cerebral artery occlusion Inhibition and genetic ablation of TRPM2 promote phosphorylation of ERK 1/2 and Akt and the inhibition of GSK3-β by Akt; TRPM2 -/mice might be protected from H 2 O 2 -induced cell death during reperfusion; TRPM2 activation promotes peripheral immune cell invasion and induces inducible nitric oxide synthase in microglia; sexually dimorphic response in TRPM2 activation is related to PARP-1 activation and ADPR formation [74][75][76] Permanent middle cerebral artery occlusion…”

The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation

“…Elevated homocysteine levels in serum have been found to mediate vascular inflammation by inducing cathepsin V expression and consequently the nuclear translocation of ERK1/2 [ 83 ]. This effect may be partially mediated by oxidative stress; treatment with selenium reverses the deleterious effects of homocysteine on endothelial cells and neuronal cells [ 117 , 118 ]. Sodium selenite has also been shown to reduce pathogenic clotting [ 119 ].…”