The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy
Summary: Epilepsy, a common central nervous system disorder, remains an enigma in pathogenesis. Emerging consensus designates hippocampal neuronal injury as a cornerstone for epileptogenic foci, pivotal in epileptic genesis and progression. Ferroptosis, a regulated cell death modality hinging on iro...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223021752 |
| _version_ | 1797659926122725376 |
|---|---|
| author | Zhen Liang Zhaoshi Zheng Qi Guo Meng Tian Jing Yang Xiu Liu Xiaojuan Zhu Songyan Liu |
| author_facet | Zhen Liang Zhaoshi Zheng Qi Guo Meng Tian Jing Yang Xiu Liu Xiaojuan Zhu Songyan Liu |
| author_sort | Zhen Liang |
| collection | DOAJ |
| description | Summary: Epilepsy, a common central nervous system disorder, remains an enigma in pathogenesis. Emerging consensus designates hippocampal neuronal injury as a cornerstone for epileptogenic foci, pivotal in epileptic genesis and progression. Ferroptosis, a regulated cell death modality hinging on iron, catalyzes lipid reactive oxygen species formation through iron and membrane polyunsaturated fatty acid interplay, culminating in oxidative cell death. This research investigates the role of hypoxia-inducible factor (HIF)-1α/heme oxygenase (HO)-1 in hippocampal neuron ferroptosis during epilepsy. Untargeted metabolomics exposes metabolite discrepancies between epilepsy patients and healthy individuals, unveiling escalated oxidative stress, heightened bilirubin, and augmented iron metabolism in epileptic blood. Enrichment analyses unveil active HIF-1 pathway in epileptic pathogenesis, reinforced by HIF-1α signaling perturbations in DisGeNET database. PTZ-kindled mice model confirms increased ferroptotic markers, oxidative stress, HIF-1α, and HO-1 in epilepsy. Study implicates HIF-1α/HO-1 potentially regulates hippocampal neuronal ferroptosis, iron metabolism, and oxidative stress, thereby promoting the propagation of epilepsy. |
| first_indexed | 2024-03-11T18:22:20Z |
| format | Article |
| id | doaj.art-9e3cac8e516c411aa2b30c916c2239a2 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T18:22:20Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-9e3cac8e516c411aa2b30c916c2239a22023-10-15T04:38:05ZengElsevieriScience2589-00422023-11-012611108098The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsyZhen Liang0Zhaoshi Zheng1Qi Guo2Meng Tian3Jing Yang4Xiu Liu5Xiaojuan Zhu6Songyan Liu7Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China; Key Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun, ChinaDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, ChinaKey Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun, ChinaKey Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun, ChinaKey Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun, ChinaKey Laboratory of Molecular Epigenetics, Ministry of Education and Institute of Cytology and Genetics, Northeast Normal University, Changchun, China; Corresponding authorDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China; Corresponding authorSummary: Epilepsy, a common central nervous system disorder, remains an enigma in pathogenesis. Emerging consensus designates hippocampal neuronal injury as a cornerstone for epileptogenic foci, pivotal in epileptic genesis and progression. Ferroptosis, a regulated cell death modality hinging on iron, catalyzes lipid reactive oxygen species formation through iron and membrane polyunsaturated fatty acid interplay, culminating in oxidative cell death. This research investigates the role of hypoxia-inducible factor (HIF)-1α/heme oxygenase (HO)-1 in hippocampal neuron ferroptosis during epilepsy. Untargeted metabolomics exposes metabolite discrepancies between epilepsy patients and healthy individuals, unveiling escalated oxidative stress, heightened bilirubin, and augmented iron metabolism in epileptic blood. Enrichment analyses unveil active HIF-1 pathway in epileptic pathogenesis, reinforced by HIF-1α signaling perturbations in DisGeNET database. PTZ-kindled mice model confirms increased ferroptotic markers, oxidative stress, HIF-1α, and HO-1 in epilepsy. Study implicates HIF-1α/HO-1 potentially regulates hippocampal neuronal ferroptosis, iron metabolism, and oxidative stress, thereby promoting the propagation of epilepsy.http://www.sciencedirect.com/science/article/pii/S2589004223021752Health sciencesMolecular biologyNeuroscienceCell biologyMetabolomics |
| spellingShingle | Zhen Liang Zhaoshi Zheng Qi Guo Meng Tian Jing Yang Xiu Liu Xiaojuan Zhu Songyan Liu The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy iScience Health sciences Molecular biology Neuroscience Cell biology Metabolomics |
| title | The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy |
| title_full | The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy |
| title_fullStr | The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy |
| title_full_unstemmed | The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy |
| title_short | The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy |
| title_sort | role of hif 1α ho 1 pathway in hippocampal neuronal ferroptosis in epilepsy |
| topic | Health sciences Molecular biology Neuroscience Cell biology Metabolomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223021752 |
| work_keys_str_mv | AT zhenliang theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT zhaoshizheng theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT qiguo theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT mengtian theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT jingyang theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT xiuliu theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT xiaojuanzhu theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT songyanliu theroleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT zhenliang roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT zhaoshizheng roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT qiguo roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT mengtian roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT jingyang roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT xiuliu roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT xiaojuanzhu roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy AT songyanliu roleofhif1aho1pathwayinhippocampalneuronalferroptosisinepilepsy |