Transient glutathione depletion in the substantia nigra compacta is associated with neuroinflammation in rats

Díaz-Hung, Mei-Li; Yglesias-Rivera, Arianna; Hernández-Zimbrón, Luis Fernando; Orozco‐Suárez, Sandra; Ruiz-Fuentes, Jenny Laura; Díaz-García, Alexis; León-Martínez, Rilda; Blanco-Lezcano, Lisette; Pavón‐Fuentes, Nancy; Pedré, Lourdes Lorigados

doi:10.1016/j.neuroscience.2016.08.023

Cited by 13 publications

(5 citation statements)

References 61 publications

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“…Furthermore, mounting data indicate that complex I inhibition by excessive Ca 2+ influx via activation of TRPM2 may cause ROS to be produced in large quantities by activating the mitochondrial permeability transition pores in neurons (Yazgan and Naziroğlu 2017;Ataizi et al 2019;An et al 2019;Ozkaya and Naziroglu 2020). Treatments with A and BSO had a comparable impact on the microglia cells' suppression of complex I (Franco et al 2008;Diaz-Hung et al 2016). BSO and Ab therapy inside the mitochondria as well as excessive Ca 2+ inflow are both known to increase ROS levels, further depolarize the mitochondrial membrane (JC-1), and produce an excessive amount of ROS.…”

Section: Discussionmentioning

confidence: 97%

Depletion of glutathione induced apoptosis and oxidative stress via the activation of TRPM2 channels in the microglia cells with Alzheimer’ disease model

Çınar

2022

Journal of Cellular Neuroscience and Oxidative Stress

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Alzheimer’s disease is a common neurodegenerative disease. Microglia induces oxidative stress in the brain for engulfing bacteria and viruses. The accumulating data indicate that oxidative stress and apoptosis are two main actors for the induction of microglia activation-induced Alzheimer’s Disease. Oxidative stress is one of many triggers that activate the transient receptor potential melastatin 2 (TRPM2) channel. Glutathione (GSH) is a main cytosolic antioxidant in the mammalian cells. The GSH depletion via the activation of TRPM2 induces oxidative stress and apoptosis in neuronal cells. It has not yet been researched how GSH depletion via activation of TRPM2 affects oxidative stress and apoptosis in microglial cells with the Alzheimer's disease model. The BV2 cells divided into 5 groups as control, buthionine sulphoximine (BSO and 0.5 mM for 6 h), amyloid beta (1 uM for 72 h), amyloid beta+BSO, and amyloid beta+BSO+GSH (10 mM for 2 h). In the BSO group, the levels of apoptosis, mitochondrial membrane potential, cytosolic free oxygen reactive species (cyROS), caspase (Casps) -3, Casps -8, and Casps -9 were increased as compared to the control group, although cell viability level was decreased. The expression levels of TRPM2, Casps -3, Casps -9, Bax, Bcl-2, and PARP-1 were also increased in the BSO group. In addition, their levels were further increased in the amyloid beta and BSO+amyloid beta groups as compared to the BSO group. However, the changes were modulated in the BSO+amyloid beta+GSH group by the incubation of GSH. In conclusion, the depletion of GSH increased apoptosis and cyROS levels via activation of caspases and TRPM2 in the amyloid beta-induced microglia cells. The treatment of GSH may be a potential target on the apoptosis and oxidative stress in the amyloid beta-induced microglia cells.

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Section: Discussionmentioning

confidence: 97%

Depletion of glutathione induced apoptosis and oxidative stress via the activation of TRPM2 channels in the microglia cells with Alzheimer’ disease model

Çınar

2022

Journal of Cellular Neuroscience and Oxidative Stress

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“…[ 55 ] In fact, depletion of GSH was demonstrated to induce degeneration of nigral dopaminergic neurons in adult rats, [ 56 ] possibly by promoting the increase of nitrosative stress. [ 57 ] By stimulating the upregulation of the transcripts of glutathione reductase ( GSR ), the enzyme which converts GSSG into GSH, the LMWPM in study can be counteracting another important PD hallmark. Accordingly, both metabolites have shown a slight tendency to decrease the GSSG/GSH ratio that is increased by MPP + .…”

Section: Discussionmentioning

confidence: 99%

Circulating (Poly)phenol Metabolites: Neuroprotection in a 3D Cell Model of Parkinson's Disease

Carecho

Figueira

Terrasso

et al. 2022

Molecular Nutrition Food Res

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Scope: Diets rich in (poly)phenols have been associated with positive effects on neurodegenerative disorders, such as Parkinson's disease (PD). Several low-molecular weight (poly)phenol metabolites (LMWPM) are found in the plasma after consumption of (poly)phenol-rich food. It is expected that LMWPM, upon reaching the brain, may have beneficial effects against both oxidative stress and neuroinflammation, and possibly attenuate cell death mechanisms relate to the loss of dopaminergic neurons in PD. Methods and Results: This study investigates the neuroprotective potential of two blood-brain barrier permeant LMWPM, catechol-O-sulfate (cat-sulf ), and pyrogallol-O-sulfate (pyr-sulf ), in a human 3D cell model of PD. Neurospheroids were generated from LUHMES neuronal precursor cells and challenged by 1-methyl-4-phenylpyridinium (MPP + ) to induce neuronal stress. LMWPM pretreatments were differently neuroprotective towards MPP + insult, presenting distinct effects on the neuronal transcriptome. Particularly, cat-sulf pretreatment appeared to boost counter-regulatory defense mechanisms (preconditioning). When MPP + is applied, both LMWPM positively modulated glutathione metabolism and heat-shock response, as also favorably shifting the balance of pro/anti-apoptotic proteins. Conclusions: Our findings point to the potential of LMWPM to trigger molecular mechanisms that help dopaminergic neurons to cope with a subsequent toxic insult. They are promising molecules to be further explored in the context of preventing and attenuating parkinsonian neurodegeneration.

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“…It has been reported that buthionine sulfoximine (BSO), a GSH synthesis inhibitor, treatment induced or worsened radiation-related disease and health risk in mice, such as cataracts 16 , brain inflammation 10 , hypertension 17 , atherosclerosis 18 , decreased HDL levels 19 , increased oxidative DNA damage 20 , and tumorigenesis 21 . Thus, induction of radiation-related disease and health risk may occur through decreased GSH levels.…”

Section: Discussionmentioning

confidence: 99%

“…GSH also has anti-inflammatory activity. Depletion of GSH promotes or enhances oxidative stress 9 , inflammatory cytokine levels 10 , and radiation-induced cell damage 11 . Previously, we analyzed changes in red blood cell (RBC) glutathione levels from 2 to 24 days after TBI in mice, finding that radiation decreased the GSH/GSSG ratio through an increase of GSSG levels and a decrease of GSH levels 7 .…”

mentioning

confidence: 99%

Total body irradiation causes a chronic decrease in antioxidant levels

Sun

Inaba

Sogo

et al. 2021

Sci Rep

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Ionizing radiation exposure may not only cause acute radiation syndrome, but also an increased risk of late effects. It has been hypothesized that induction of chronic oxidative stress mediates the late effects of ionizing radiation. However, only a few reports have analyzed changes in long-term antioxidant capacity after irradiation in vivo. Our previous study demonstrated changes in whole-blood antioxidant capacity and red blood cell (RBC) glutathione levels within 50 days after total body irradiation (TBI). In this study, seven-week-old, male, C57BL/6J mice exposed to total body irradiation by X-ray and changes in whole-blood antioxidant capacity and RBC glutathione levels at ≥ 100 days after TBI were investigated. Whole-blood antioxidant capacity was chronically decreased in the 5-Gy group. The RBC reduced glutathione (GSH) level and the GSH/oxidative glutathione (GSSG) ratio were chronically decreased after ≥ 1 Gy of TBI. Interestingly, the complete blood counts (CBC) changed less with 1-Gy exposure, suggesting that GSH and the GSH/GSSG ratio were more sensitive radiation exposure markers than whole-blood antioxidant capacity and CBC counts. It has been reported that GSH depletion is one of the triggers leading to cataracts, hypertension, and atherosclerosis, and these diseases are also known as radiation-induced late effects. The present findings further suggest that chronic antioxidant reduction may contribute to the pathogenesis of late radiation effects.

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Transient glutathione depletion in the substantia nigra compacta is associated with neuroinflammation in rats

Cited by 13 publications

References 61 publications

Depletion of glutathione induced apoptosis and oxidative stress via the activation of TRPM2 channels in the microglia cells with Alzheimer’ disease model

Depletion of glutathione induced apoptosis and oxidative stress via the activation of TRPM2 channels in the microglia cells with Alzheimer’ disease model

Circulating (Poly)phenol Metabolites: Neuroprotection in a 3D Cell Model of Parkinson's Disease

Total body irradiation causes a chronic decrease in antioxidant levels

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