Ferroptosis Contributes to Isoflurane Neurotoxicity
The underlying mechanisms of isoflurane neurotoxicity in the developing brain remain unclear. Ferroptosis is a recently characterized form of programmed cell death distinct from apoptosis or autophagy, characterized by iron-dependent reactive oxygen species (ROS) generation secondary to failure of g...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00486/full |
| _version_ | 1819067156923416576 |
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| author | Yimeng Xia Yimeng Xia Xiaoyun Sun Yan Luo Creed M. Stary |
| author_facet | Yimeng Xia Yimeng Xia Xiaoyun Sun Yan Luo Creed M. Stary |
| author_sort | Yimeng Xia |
| collection | DOAJ |
| description | The underlying mechanisms of isoflurane neurotoxicity in the developing brain remain unclear. Ferroptosis is a recently characterized form of programmed cell death distinct from apoptosis or autophagy, characterized by iron-dependent reactive oxygen species (ROS) generation secondary to failure of glutathione-dependent antioxidant defenses. The results of the present study are the first to demonstrate in vitro that ferroptosis is a central mechanism contributing to isoflurane neurotoxicity. We observed in embryonic mouse primary cortical neuronal cultures (day-in-vitro 7) that 6 h of 2% isoflurane exposure was associated with decreased transcription and protein expression of the lipid repair enzyme glutathione peroxidase 4. In parallel, isoflurane exposure resulted in increased ROS generation, disruption in mitochondrial membrane potential, and cell death. These effects were significantly attenuated by pre-treatment with the selective ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, these observations provide a novel mechanism for isoflurane-induced injury in the developing brain and suggest that pre-treatment with Fer-1 may be a potential clinical intervention for neuroprotection. |
| first_indexed | 2024-12-21T16:13:47Z |
| format | Article |
| id | doaj.art-0eb20c9885304477ab0cdd931af22819 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-21T16:13:47Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-0eb20c9885304477ab0cdd931af228192022-12-21T18:57:45ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-01-011110.3389/fnmol.2018.00486424815Ferroptosis Contributes to Isoflurane NeurotoxicityYimeng Xia0Yimeng Xia1Xiaoyun Sun2Yan Luo3Creed M. Stary4Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United StatesThe underlying mechanisms of isoflurane neurotoxicity in the developing brain remain unclear. Ferroptosis is a recently characterized form of programmed cell death distinct from apoptosis or autophagy, characterized by iron-dependent reactive oxygen species (ROS) generation secondary to failure of glutathione-dependent antioxidant defenses. The results of the present study are the first to demonstrate in vitro that ferroptosis is a central mechanism contributing to isoflurane neurotoxicity. We observed in embryonic mouse primary cortical neuronal cultures (day-in-vitro 7) that 6 h of 2% isoflurane exposure was associated with decreased transcription and protein expression of the lipid repair enzyme glutathione peroxidase 4. In parallel, isoflurane exposure resulted in increased ROS generation, disruption in mitochondrial membrane potential, and cell death. These effects were significantly attenuated by pre-treatment with the selective ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, these observations provide a novel mechanism for isoflurane-induced injury in the developing brain and suggest that pre-treatment with Fer-1 may be a potential clinical intervention for neuroprotection.https://www.frontiersin.org/article/10.3389/fnmol.2018.00486/fullglutathione peroxidaseferrostatin-1ironreactive oxygen speciesmitochondriavolatile anesthetic |
| spellingShingle | Yimeng Xia Yimeng Xia Xiaoyun Sun Yan Luo Creed M. Stary Ferroptosis Contributes to Isoflurane Neurotoxicity Frontiers in Molecular Neuroscience glutathione peroxidase ferrostatin-1 iron reactive oxygen species mitochondria volatile anesthetic |
| title | Ferroptosis Contributes to Isoflurane Neurotoxicity |
| title_full | Ferroptosis Contributes to Isoflurane Neurotoxicity |
| title_fullStr | Ferroptosis Contributes to Isoflurane Neurotoxicity |
| title_full_unstemmed | Ferroptosis Contributes to Isoflurane Neurotoxicity |
| title_short | Ferroptosis Contributes to Isoflurane Neurotoxicity |
| title_sort | ferroptosis contributes to isoflurane neurotoxicity |
| topic | glutathione peroxidase ferrostatin-1 iron reactive oxygen species mitochondria volatile anesthetic |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00486/full |
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