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Title:
Characterization of Selenium Compounds for Anti-ferroptotic Activity in Neuronal Cells and After Cerebral Ischemia–Reperfusion Injury | Neurotherapeutics
Description:
The emergence of ferroptosis as a cell death pathway associated with brain disorders including stroke and neurodegenerative diseases emphasizes the need to develop therapeutics able to target the brain and to protect neurons from ferroptotic death. Selenium plays an essential role in reducing lipid peroxidation generated during ferroptosis through its incorporation into the catalytic site of glutathione peroxidase 4. Here, we compared the anti-ferroptotic activity of several organic and inorganic selenium compounds: methylselenocysteine, selenocystine, selenomethionine, selenocystamine, ebselen, sodium selenite, and sodium selenate. All were effective against erastin- and RSL3-induced ferroptosis in vitro. We characterized the ability of the selenium compounds to release selenium and boost glutathione peroxidase expression and activity. Based on our results, we selected organic selenium compounds of similar characteristics and investigated their effectiveness in protecting against neuronal death in vivo using the cerebral ischemia–reperfusion injury mouse model. We found that pretreatment with methylselenocysteine or selenocystamine provided protection from ischemia–reperfusion neuronal damage in vivo. These data support the use of ferroptosis inhibitors for treatment and select selenium compounds for prevention of neuronal damage in ischemic stroke and other diseases of the brain where ferroptosis is implicated.
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Keywords {🔍}
selenium, ferroptosis, gpx, selenocompounds, article, activity, cell, google, scholar, fig, cas, cells, antiferroptotic, methylselenocysteine, ebselen, neuronal, mice, data, protein, compounds, selenocystamine, brain, expression, model, ischemiareperfusion, stroke, glutathione, treatment, increase, volume, mcao, injury, death, organic, ischemic, induced, cerebral, selenocystine, selenomethionine, levels, peroxidase, cancer, infarct, supplementary, research, pdf, inorganic, vitro, prevention, animal,
Topics {✒️}
abdel ali belaidi cerebral ischemia–reperfusion injury ischemia–reperfusion injury prevents rescuing ischemia–reperfusion injury post-doctor research project preventing gpx4-mediated clearance ischemia–reperfusion neuronal damage friedmann angeli jp antioxidant/radical trapping agent ice-cold lysis buffer robust anti-ferroptotic activity malin-deficient mouse model stronger anti-ferroptotic activity similar anti-ferroptotic properties selenium-dependent glutathione peroxidase cystine/glutamate antiporter system focal cerebral ischemia methyl-s-cys = methylselenocysteine 5 mg/kg body weight 60 mg/kg body weight mcao-induced ischemic injury mouse anti-β-actin ischemia–reperfusion injury potent anti-ferroptotic response showed anti-ferroptotic activity iron-dependent catalytic mechanisms prevent hydroperoxide-induced ferroptosis atypical dose–response curve peng lei neurological assessment post-surgery redox biology privacy choices/manage cookies anti-ferroptotic compound anti-ferroptotic genes article tuo state key laboratory preventing ferroptotic death attenuate neuronal damage anti-ferroptotic activity common carotid artery anti-ferroptotic compounds cellular selenium levels anti-ferroptotic activities neuronal cell model western blot analysis methods cell culture nat cell biol cell death pathway preventing neuronal death attenuate neurological deficits
Questions {❓}
- Glutathione peroxidase 4: a new player in neurodegeneration?
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headline:Characterization of Selenium Compounds for Anti-ferroptotic Activity in Neuronal Cells and After Cerebral Ischemia–Reperfusion Injury
description:The emergence of ferroptosis as a cell death pathway associated with brain disorders including stroke and neurodegenerative diseases emphasizes the need to develop therapeutics able to target the brain and to protect neurons from ferroptotic death. Selenium plays an essential role in reducing lipid peroxidation generated during ferroptosis through its incorporation into the catalytic site of glutathione peroxidase 4. Here, we compared the anti-ferroptotic activity of several organic and inorganic selenium compounds: methylselenocysteine, selenocystine, selenomethionine, selenocystamine, ebselen, sodium selenite, and sodium selenate. All were effective against erastin- and RSL3-induced ferroptosis in vitro. We characterized the ability of the selenium compounds to release selenium and boost glutathione peroxidase expression and activity. Based on our results, we selected organic selenium compounds of similar characteristics and investigated their effectiveness in protecting against neuronal death in vivo using the cerebral ischemia–reperfusion injury mouse model. We found that pretreatment with methylselenocysteine or selenocystamine provided protection from ischemia–reperfusion neuronal damage in vivo. These data support the use of ferroptosis inhibitors for treatment and select selenium compounds for prevention of neuronal damage in ischemic stroke and other diseases of the brain where ferroptosis is implicated.
datePublished:2021-09-08T00:00:00Z
dateModified:2021-09-08T00:00:00Z
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keywords:
Selenium
Glutathione peroxidase
Ferroptosis
Glutathione
Ischemia–reperfusion injury
Neurosciences
Neurology
Neurosurgery
Neurobiology
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headline:Characterization of Selenium Compounds for Anti-ferroptotic Activity in Neuronal Cells and After Cerebral Ischemia–Reperfusion Injury
description:The emergence of ferroptosis as a cell death pathway associated with brain disorders including stroke and neurodegenerative diseases emphasizes the need to develop therapeutics able to target the brain and to protect neurons from ferroptotic death. Selenium plays an essential role in reducing lipid peroxidation generated during ferroptosis through its incorporation into the catalytic site of glutathione peroxidase 4. Here, we compared the anti-ferroptotic activity of several organic and inorganic selenium compounds: methylselenocysteine, selenocystine, selenomethionine, selenocystamine, ebselen, sodium selenite, and sodium selenate. All were effective against erastin- and RSL3-induced ferroptosis in vitro. We characterized the ability of the selenium compounds to release selenium and boost glutathione peroxidase expression and activity. Based on our results, we selected organic selenium compounds of similar characteristics and investigated their effectiveness in protecting against neuronal death in vivo using the cerebral ischemia–reperfusion injury mouse model. We found that pretreatment with methylselenocysteine or selenocystamine provided protection from ischemia–reperfusion neuronal damage in vivo. These data support the use of ferroptosis inhibitors for treatment and select selenium compounds for prevention of neuronal damage in ischemic stroke and other diseases of the brain where ferroptosis is implicated.
datePublished:2021-09-08T00:00:00Z
dateModified:2021-09-08T00:00:00Z
pageStart:2682
pageEnd:2691
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Selenium
Glutathione peroxidase
Ferroptosis
Glutathione
Ischemia–reperfusion injury
Neurosciences
Neurology
Neurosurgery
Neurobiology
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