Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1
BackgroundOxidative stress enhances tumor invasion and metastasis in brain cancer. The activation of divalent metal transporter 1 (DMT1), which is regulated by glutamate receptors, can result in the increase of oxidative stress and risk of cancer development. Propofol, an anesthetic with antioxidant...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.590931/full |
| _version_ | 1828782291115048960 |
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| author | Chenyi Yang Chenyi Yang Zhengyuan Xia Tang Li Tang Li Yimeng Chen Yimeng Chen Mingshu Zhao Mingshu Zhao Yi Sun Yi Sun Ji Ma Ji Ma Yi Wu Yi Wu Xinyue Wang Xinyue Wang Peng Wang Haiyun Wang Haiyun Wang |
| author_facet | Chenyi Yang Chenyi Yang Zhengyuan Xia Tang Li Tang Li Yimeng Chen Yimeng Chen Mingshu Zhao Mingshu Zhao Yi Sun Yi Sun Ji Ma Ji Ma Yi Wu Yi Wu Xinyue Wang Xinyue Wang Peng Wang Haiyun Wang Haiyun Wang |
| author_sort | Chenyi Yang |
| collection | DOAJ |
| description | BackgroundOxidative stress enhances tumor invasion and metastasis in brain cancer. The activation of divalent metal transporter 1 (DMT1), which is regulated by glutamate receptors, can result in the increase of oxidative stress and risk of cancer development. Propofol, an anesthetic with antioxidant capacity, has been shown to decrease oxidative stress in several different types of cancer. However, the underlying mechanism remains unclear. Therefore, the present study aimed to elucidate the mechanism underlying the suppression of oxidative stress in glioma cells by propofol. It was hypothesized that propofol may inhibit oxidative stress in gliomas via suppressing Ca2+-permeable α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA) receptor (CPAR)-DMT1 signaling.MethodsMale Wistar rats with C6 gliomas, which were established by intracranial injection of C6 glioma cells, were either treated with propofol or not for 6 h before being sacrificed. The levels of AMPA receptor subunit GluR2 and DMT1 protein expression were assessed using western blotting. The association between CPARs and DMT1 was confirmed in vitro using the AMPA receptor activator (R, S)-AMPA. Glutathione and reactive oxygen species assay kits were used to evaluate tumor oxidative stress. The effect of propofol on glioma proliferation was evaluated by determining tumor weight, cell cycles and a growth curve.ResultsPropofol infusion at either 20 or 40 mg/kg-1/h-1 increased GluR2 levels and downregulated DMT1 expression as well as glutathione content markedly in the periphery compared with that in the glioma core. The in vitro results revealed that (R, S)-AMPA increased DMT1 expression and reactive oxygen species levels, which were partly reversed by propofol treatment.ConclusionPropofol regulated DMT1 expression by modulating CPARs, resulting in the inhibition of tumor oxidative stress and glioma growth. The present study provides evidence for optimizing the selection of anesthetic drugs in perioperative management and prognosis of patients with glioma. |
| first_indexed | 2024-12-11T17:46:33Z |
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| id | doaj.art-798ba67eb99e4ae5bf5c8cb840304773 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T17:46:33Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-798ba67eb99e4ae5bf5c8cb8403047732022-12-22T00:56:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-11-011010.3389/fonc.2020.590931590931Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1Chenyi Yang0Chenyi Yang1Zhengyuan Xia2Tang Li3Tang Li4Yimeng Chen5Yimeng Chen6Mingshu Zhao7Mingshu Zhao8Yi Sun9Yi Sun10Ji Ma11Ji Ma12Yi Wu13Yi Wu14Xinyue Wang15Xinyue Wang16Peng Wang17Haiyun Wang18Haiyun Wang19Department of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The University of Hong Kong, Hong Kong, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaDepartment of Anesthesiology, The Third Central Hospital of Tianjin, Nankai University Affinity the Third Central Hospital, The Third Central Clinical College of Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaBackgroundOxidative stress enhances tumor invasion and metastasis in brain cancer. The activation of divalent metal transporter 1 (DMT1), which is regulated by glutamate receptors, can result in the increase of oxidative stress and risk of cancer development. Propofol, an anesthetic with antioxidant capacity, has been shown to decrease oxidative stress in several different types of cancer. However, the underlying mechanism remains unclear. Therefore, the present study aimed to elucidate the mechanism underlying the suppression of oxidative stress in glioma cells by propofol. It was hypothesized that propofol may inhibit oxidative stress in gliomas via suppressing Ca2+-permeable α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA) receptor (CPAR)-DMT1 signaling.MethodsMale Wistar rats with C6 gliomas, which were established by intracranial injection of C6 glioma cells, were either treated with propofol or not for 6 h before being sacrificed. The levels of AMPA receptor subunit GluR2 and DMT1 protein expression were assessed using western blotting. The association between CPARs and DMT1 was confirmed in vitro using the AMPA receptor activator (R, S)-AMPA. Glutathione and reactive oxygen species assay kits were used to evaluate tumor oxidative stress. The effect of propofol on glioma proliferation was evaluated by determining tumor weight, cell cycles and a growth curve.ResultsPropofol infusion at either 20 or 40 mg/kg-1/h-1 increased GluR2 levels and downregulated DMT1 expression as well as glutathione content markedly in the periphery compared with that in the glioma core. The in vitro results revealed that (R, S)-AMPA increased DMT1 expression and reactive oxygen species levels, which were partly reversed by propofol treatment.ConclusionPropofol regulated DMT1 expression by modulating CPARs, resulting in the inhibition of tumor oxidative stress and glioma growth. The present study provides evidence for optimizing the selection of anesthetic drugs in perioperative management and prognosis of patients with glioma.https://www.frontiersin.org/articles/10.3389/fonc.2020.590931/fullgliomapropofoldivalent metal transporter 1α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptoroxidative stress |
| spellingShingle | Chenyi Yang Chenyi Yang Zhengyuan Xia Tang Li Tang Li Yimeng Chen Yimeng Chen Mingshu Zhao Mingshu Zhao Yi Sun Yi Sun Ji Ma Ji Ma Yi Wu Yi Wu Xinyue Wang Xinyue Wang Peng Wang Haiyun Wang Haiyun Wang Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1 Frontiers in Oncology glioma propofol divalent metal transporter 1 α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor oxidative stress |
| title | Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1 |
| title_full | Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1 |
| title_fullStr | Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1 |
| title_full_unstemmed | Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1 |
| title_short | Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1 |
| title_sort | antioxidant effect of propofol in gliomas and its association with divalent metal transporter 1 |
| topic | glioma propofol divalent metal transporter 1 α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.590931/full |
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