Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress

Ergül, Mustafa; Taşkıran, Ahmet Şevki

doi:10.1248/cpb.c21-00169

Cited by 10 publications

(10 citation statements)

References 35 publications

(40 reference statements)

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“…Ergul et al. identified that thiamine protected glioblastoma cells against glutamate toxicity by inhibiting ATF4-associated endoplasmic reticulum stress ( 49 ). Recently, a TRAIL-inducing compound ONC201/TIC10 was found to promote apoptosis and integrated stress response in multiple tumors by activating ATF4 ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Zhang

Chen

et al. 2022

Front. Oncol.

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ObjectiveTo clarify the function and mechanisms of sevoflurane (Sev) on ferroptosis in glioma cells.MethodsDifferent concentrations of Sev were used to treat glioma cells U87 and U251. Ferroptosis inducer Erastin was used to incubate glioma cells combined with Sev and ATF4 siRNA transfection treatment. CCK-8 assay and colorimetric assay were performed to analyze cell viability and Fe+ concentration, respectively. The releases of reactive oxygen species (ROS) were determined by flow cytometry analysis. Transcriptional sequencing was used to screen the differential genes affected by Sev in U251 cells. The mRNA and protein expression of ferroptosis-associated genes was detected by qRT-PCR and Western blotting.ResultsSev could suppress cell viability, increase ROS levels and Fe+ concentration, downregulate the protein expression levels of GPX4, and upregulate transferrin, ferritin, and Beclin-1 in a dose-dependent manner in U87 and U251 cells. The expression of ferroptosis and mitophagy-related gene activating transcription factor 4 (ATF4) was identified to be enhanced by Sev analyzed by transcriptional sequencing. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), which is involved in ferroptosis, is a downstream gene of ATF4. Inhibition of ATF4 could interrupt the expression of CHAC1 induced by Sev in U87 and U251 cells. Ferroptosis inducer Erastin treatment obviously inhibited the cell viability, elevated the Fe2+ concentration, and promoted ROS generation in U87 and U251 cells. The protein level of ATF4 and CHAC1 was increased in Erastin-treated U87 and U251 cells. Moreover, the interruption of Sev-induced ferroptosis and CHAC1 activating induced by ATF4 suppression could be reversed by Erastin.ConclusionsIn summary, this study suggested that Sev exposure-induced ferroptosis by the ATF4-CHAC1 pathway in glioma cells.

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Section: Discussionmentioning

confidence: 99%

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Zhang

Chen

et al. 2022

Front. Oncol.

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“…Since glutamate receptor subtypes (ionotropic and metabotropic) are expressed in C6 glioblastoma cells, these cells can be a beneficial model for investigating excitotoxicity [ 18 ]. Moreover, C6 glial cells provide physical and metabolic support to the survival of neurons, such as insulation and communication of neurons and transportation of nutrients and waste; hence, glial cell damage may play role in the neurodegeneration process.…”

Section: Discussionmentioning

confidence: 99%

Cuscuta epithymum Murr. crude extract pre-conditioning protects C6 cells from L-glutamate-induced neurotoxicity

Pourhadi

Niknam

Ghasemi

et al. 2022

BMC Complement Med Ther

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Background Cuscuta epithymum Murr. (C. epithymum), as an herbal medicine, has played an anti-cancerous role in various studies; however, its possible neuroprotective effects have been neglected. Here, we aimed to investigate the protective effects of C. epithymum seeds crude extract and different fractions on rat glioblastoma cells (C6) in L-glutamate oxidative condition. Methods Initially, the total phenolic content of C. epithymum crude extract and the fractions (all produced by maceration method) was determined. Subsequently, C6 cells were pre-treated with the various concentrations of crude extract and fractions 24 h before L-glutamate exposure. Likewise, C6 cells were treated with the same concentrations of crude extract and fractions 24 h after exposure to L-glutamate. The cell viability and morphology were compared in crude extract and fractions groups, then superoxide dismutase (SODs) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) levels were measured. The flow cytometry test was used to study C. epithymum crude extract's effects on the cell cycle and also to quantify the apoptosis, necrosis, and live cells population in different groups. Results C. epithymum crude extract and fractions (hexanoic, dichloromethanolic, and methanolic) had concentration-dependent cytotoxicity (IC50:126.47, 2101.96, 140.97, and 218.96 µg/ml, respectively). The crude extract and methanolic fraction contained phenolic compounds (55.99 ± 2.795 and 50.80 ± 2.969 mg gallic acid/g extract), while in hexanoic and dichloromethanolic fractions, the phenolic content was undetectable. In the cell viability assay, in comparison to fractions, the crude extract showed a more protective effect against glutamate-induced oxidative condition (P < 0.0001). The crude extract increased the SODs activity (P < 0.001) and decreased MDA and ROS levels (P < 0.0001) in comparison to the glutamate group. The crude extract significantly increased the population of cells in G1 (from 63.04 to 76.29) and decreased the percentage of cells in G2 (from 11.56 to 6.7) and S phase (from 25.4 to 17.01). In addition, it decreased the apoptotic and necrotic cell populations (from 34 to 17.1) and also increased the percentage of live cells (from 66.8 to 83.4 percent) in the flow cytometry test. Conclusion C. epithymum crude extract plays a neuroprotective role by activating the defense mechanisms in cell against the oxidative condition.

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“…São necessárias para sustentar a glicose e aminoácidos no organismo. Além disso a tiamina é um fator benéfico para cada indivíduo, considerada micronutriente essencial no organismo humano (Ergül & Taşkıran, 2021).…”

Section: Vitaminas Do Complexo Bunclassified

Como evitar perdas de vitaminas essenciais durante processamento dos alimentos

Silva

Santana

Gomes

et al. 2022

RSD

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Micronutrientes vitamínicos são primordiais para o corpo humano. Vitaminas hidrossolúveis são classificadas como vitaminas do complexo B (B1, B2, B3, B6, B9, B12) e Vitamina C. A carência dessas vitaminas pode originar doenças que prejudicam a saúde humana, como a anemia perniciosa e pelagra. Durante o tratamento térmico essas vitaminas acabam se perdendo. Devido a Pandemia do Covid-19, indústrias brasileiras aumentaram a exportação de frutos ricos em vitamina C, como laranja e limão em 132 % e 12 %, respectivamente. Com ajuda de pesquisadores as indústrias têm potencial para elaborar suplementos adequados para fornecer energia necessária para o organismo humano. Dessa forma, objetivou-se fazer um levantamento de trabalhos que relatam as perdas de vitamina B e C durante o processamento. Percebe-se que vários alimentos tem propriedades antioxidantes devido a presença de nutrientes vitamínicos, sendo imprescindível para o organismo, pois sua função impossibilita a oxidação celular e favorece na defesa contra radicais livres. Dentre os métodos de processamento de alimentos, a microencapsulação e liofilização são bastante eficazes na preservação de componentes bioativas das vitaminas.

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Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress

Cited by 10 publications

References 35 publications

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway

Cuscuta epithymum Murr. crude extract pre-conditioning protects C6 cells from L-glutamate-induced neurotoxicity

Como evitar perdas de vitaminas essenciais durante processamento dos alimentos

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