Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression
ABSTRACTThis study examined the effects of methyltransferase-like 3 (METTL3) on ferroptosis during intracerebral hemorrhage (ICH) progression. The brain microvascular endothelial cells (BMVECs) were stimulated with oxygen and glucose deprivation (OGD) and hemin to establish an ICH model. Cell viabil...
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| Format: | Article |
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Taylor & Francis Group
2022-06-01
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| Series: | Bioengineered |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21655979.2022.2084494 |
| _version_ | 1811175387533672448 |
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| author | Liu Zhang Xiangyu Wang Wenqiang Che Yongjun Yi Shuoming Zhou Yongjian Feng |
| author_facet | Liu Zhang Xiangyu Wang Wenqiang Che Yongjun Yi Shuoming Zhou Yongjian Feng |
| author_sort | Liu Zhang |
| collection | DOAJ |
| description | ABSTRACTThis study examined the effects of methyltransferase-like 3 (METTL3) on ferroptosis during intracerebral hemorrhage (ICH) progression. The brain microvascular endothelial cells (BMVECs) were stimulated with oxygen and glucose deprivation (OGD) and hemin to establish an ICH model. Cell viability was tested using a CCK8 assay. The levels of Fe2+, glutathione, reactive oxygen species, LPO, and MDA were determined using the corresponding commercial kits. Cell death was analyzed using TUNEL and propidium iodide staining. The correlation between METTL3 and glutathione peroxidase 4 (GPX4) was analyzed using Spearman’s correlation test and further confirmed using the CHIP assay. Western blotting and RT-qPCR were performed to measure the relative expression levels. Mice were injected with 0.2 units collagenase IV to establish an ICH model in vivo. We found that the Fe2+, reactive oxygen species, LPO, and MDA levels were enhanced, and glutathione was depleted in OGD/H-treated BMVECs as well as in ICH mice. Additionally, cell viability and SLC7A11 protein levels decreased, and cell death and TFR1 protein levels increased in OGD/H-treated BMVECs. METTL3 silencing relieves OGD/H-induced injury in BMVECs. In addition, METTL3 was significantly negatively related to GPX4, which was further confirmed by the CHIP assay. Silencing of METTL3 decreased the N6-methyladenosine levels of GPX4 and increased its mRNA levels of GPX4. GPX4 knockdown neutralized the role of METTL3 in OGD/H-treated BMVECs. These results implied that ferroptosis occurred in the ODG/H-treated BMVECs and ICH mouse models. METTL3 silencing effectively suppressed ferroptosis by regulating N6-methyladenosine and mRNA levels of GPX4. |
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| institution | Directory Open Access Journal |
| issn | 2165-5979 2165-5987 |
| language | English |
| last_indexed | 2024-04-10T19:36:22Z |
| publishDate | 2022-06-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Bioengineered |
| spelling | doaj.art-3130e1694df348f4810b981c026bac0a2023-01-30T05:01:59ZengTaylor & Francis GroupBioengineered2165-59792165-59872022-06-01136142151422610.1080/21655979.2022.2084494Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progressionLiu Zhang0Xiangyu Wang1Wenqiang Che2Yongjun Yi3Shuoming Zhou4Yongjian Feng5Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaABSTRACTThis study examined the effects of methyltransferase-like 3 (METTL3) on ferroptosis during intracerebral hemorrhage (ICH) progression. The brain microvascular endothelial cells (BMVECs) were stimulated with oxygen and glucose deprivation (OGD) and hemin to establish an ICH model. Cell viability was tested using a CCK8 assay. The levels of Fe2+, glutathione, reactive oxygen species, LPO, and MDA were determined using the corresponding commercial kits. Cell death was analyzed using TUNEL and propidium iodide staining. The correlation between METTL3 and glutathione peroxidase 4 (GPX4) was analyzed using Spearman’s correlation test and further confirmed using the CHIP assay. Western blotting and RT-qPCR were performed to measure the relative expression levels. Mice were injected with 0.2 units collagenase IV to establish an ICH model in vivo. We found that the Fe2+, reactive oxygen species, LPO, and MDA levels were enhanced, and glutathione was depleted in OGD/H-treated BMVECs as well as in ICH mice. Additionally, cell viability and SLC7A11 protein levels decreased, and cell death and TFR1 protein levels increased in OGD/H-treated BMVECs. METTL3 silencing relieves OGD/H-induced injury in BMVECs. In addition, METTL3 was significantly negatively related to GPX4, which was further confirmed by the CHIP assay. Silencing of METTL3 decreased the N6-methyladenosine levels of GPX4 and increased its mRNA levels of GPX4. GPX4 knockdown neutralized the role of METTL3 in OGD/H-treated BMVECs. These results implied that ferroptosis occurred in the ODG/H-treated BMVECs and ICH mouse models. METTL3 silencing effectively suppressed ferroptosis by regulating N6-methyladenosine and mRNA levels of GPX4.https://www.tandfonline.com/doi/10.1080/21655979.2022.2084494Intracerebral hemorrhageMETTL3GPX4ferroptosis |
| spellingShingle | Liu Zhang Xiangyu Wang Wenqiang Che Yongjun Yi Shuoming Zhou Yongjian Feng Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression Bioengineered Intracerebral hemorrhage METTL3 GPX4 ferroptosis |
| title | Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression |
| title_full | Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression |
| title_fullStr | Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression |
| title_full_unstemmed | Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression |
| title_short | Methyltransferase-like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression |
| title_sort | methyltransferase like 3 silenced inhibited the ferroptosis development via regulating the glutathione peroxidase 4 levels in the intracerebral hemorrhage progression |
| topic | Intracerebral hemorrhage METTL3 GPX4 ferroptosis |
| url | https://www.tandfonline.com/doi/10.1080/21655979.2022.2084494 |
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