Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity
Central nervous system (CNS) oxygen toxicity (CNS-OT) is a toxic reaction that appears after the inhalation of gas at an excessive oxygen partial pressure during underwater operation or hyperbaric oxygen (HBO) treatment. The mechanism of CNS-OT has not been clearly characterized. Though it has been...
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.596326/full |
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| author | Yanan Zhang Benming You Yuliang Chen Junlin Yang Chengwei Xie Guoyang Huang Runping Li Ping Hu Ping Hu Ping Hu Ping Hu Ping Hu |
| author_facet | Yanan Zhang Benming You Yuliang Chen Junlin Yang Chengwei Xie Guoyang Huang Runping Li Ping Hu Ping Hu Ping Hu Ping Hu Ping Hu |
| author_sort | Yanan Zhang |
| collection | DOAJ |
| description | Central nervous system (CNS) oxygen toxicity (CNS-OT) is a toxic reaction that appears after the inhalation of gas at an excessive oxygen partial pressure during underwater operation or hyperbaric oxygen (HBO) treatment. The mechanism of CNS-OT has not been clearly characterized. Though it has been attributed to the excessive oxidative stress induced by HBO, evidences against this hypothesis have been reported. Here we find that Forkhead box protein O3 (FoxO3a) is important for CNS-OT protection. FoxO3a knock-out (KO) mice had a shorter latency to develop convulsions and greater number of seizures within a certain period of time. The acute lung injury (ALI) induced by CNS-OT was also more severe in FoxO3a KO mice. Further analysis reveals a significant decrease in the activity of catalase (CAT), an antioxidant enzyme and a significant increase in the content of malondialdehyde (MDA), an oxidative product, in brain tissues of FoxO3a KO mice. Short-time HBO exposure could increase FoxO3a expression level and trigger its nuclear translocation. The level of nuclear localized FoxO3a peaked at 8 h after exposure. Our results demonstrate that the activity of FoxO3a is highly sensitive to HBO exposure and FoxO3a plays important roles in protecting CNS-OT. Further mechanic analysis reveals that FoxO3a protects CNS-OT via activating antioxidative signaling pathway. |
| first_indexed | 2024-12-17T05:55:41Z |
| format | Article |
| id | doaj.art-35af2b1192c34022b40fd5a048b7d574 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-17T05:55:41Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-35af2b1192c34022b40fd5a048b7d5742022-12-21T22:01:02ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-12-011110.3389/fphys.2020.596326596326Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen ToxicityYanan Zhang0Benming You1Yuliang Chen2Junlin Yang3Chengwei Xie4Guoyang Huang5Runping Li6Ping Hu7Ping Hu8Ping Hu9Ping Hu10Ping Hu11Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Navy Medical University, Shanghai, ChinaDepartment of Pharmacy, Changhai Hospital, Navy Medical University, Shanghai, ChinaDepartment of Nautical and Aviation Medicine Center, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, ChinaXinhua Hospital, Shangahai Jiao Tong University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Navy Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Navy Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Navy Medical University, Shanghai, ChinaState Key Laboratory of Cell Biology, Center of Excellence in Molecular and Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, ChinaInstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, ChinaBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, ChinaXinhua Hospital, Shangahai Jiao Tong University, Shanghai, ChinaShanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, ChinaCentral nervous system (CNS) oxygen toxicity (CNS-OT) is a toxic reaction that appears after the inhalation of gas at an excessive oxygen partial pressure during underwater operation or hyperbaric oxygen (HBO) treatment. The mechanism of CNS-OT has not been clearly characterized. Though it has been attributed to the excessive oxidative stress induced by HBO, evidences against this hypothesis have been reported. Here we find that Forkhead box protein O3 (FoxO3a) is important for CNS-OT protection. FoxO3a knock-out (KO) mice had a shorter latency to develop convulsions and greater number of seizures within a certain period of time. The acute lung injury (ALI) induced by CNS-OT was also more severe in FoxO3a KO mice. Further analysis reveals a significant decrease in the activity of catalase (CAT), an antioxidant enzyme and a significant increase in the content of malondialdehyde (MDA), an oxidative product, in brain tissues of FoxO3a KO mice. Short-time HBO exposure could increase FoxO3a expression level and trigger its nuclear translocation. The level of nuclear localized FoxO3a peaked at 8 h after exposure. Our results demonstrate that the activity of FoxO3a is highly sensitive to HBO exposure and FoxO3a plays important roles in protecting CNS-OT. Further mechanic analysis reveals that FoxO3a protects CNS-OT via activating antioxidative signaling pathway.https://www.frontiersin.org/articles/10.3389/fphys.2020.596326/fullhyperbaric oxygenoxygen toxicitycentral nervous systemFoxO3aoxidative stress |
| spellingShingle | Yanan Zhang Benming You Yuliang Chen Junlin Yang Chengwei Xie Guoyang Huang Runping Li Ping Hu Ping Hu Ping Hu Ping Hu Ping Hu Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity Frontiers in Physiology hyperbaric oxygen oxygen toxicity central nervous system FoxO3a oxidative stress |
| title | Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity |
| title_full | Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity |
| title_fullStr | Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity |
| title_full_unstemmed | Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity |
| title_short | Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity |
| title_sort | effect of transcriptional regulatory factor foxo3a on central nervous system oxygen toxicity |
| topic | hyperbaric oxygen oxygen toxicity central nervous system FoxO3a oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2020.596326/full |
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