ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke
Rong Huang,1 Xiaoyan Huang,1 Hongmei Yang,1 Haixuan Wu,1 Fan Liu,1 Phei Er Saw,2,3 Minghui Cao1,4 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-02-01
|
| Series: | Biologics: Targets & Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/atf3-knockdown-exacerbates-astrocyte-activation-by-inhibiting-phosphor-peer-reviewed-fulltext-article-BTT |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823858005435744256 |
|---|---|
| author | Huang R Huang X Yang H Wu H Liu F Saw PE Cao M |
| author_facet | Huang R Huang X Yang H Wu H Liu F Saw PE Cao M |
| author_sort | Huang R |
| collection | DOAJ |
| description | Rong Huang,1 Xiaoyan Huang,1 Hongmei Yang,1 Haixuan Wu,1 Fan Liu,1 Phei Er Saw,2,3 Minghui Cao1,4 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 4Department of Anesthesiology, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, People’s Republic of ChinaCorrespondence: Phei Er Saw; Minghui Cao, Email caipeie@mail.sysu.edu.cn; caomh@mail.sysu.edu.cnIntroduction: ATF3, a stress-induced transcription factor, has been implicated in the injury processes of various cell types, including neurons. It is recognized as a common marker for neuronal damage following neurotrauma. However, its role in other types of glial cells, particularly astrocytes, in response to ischemic injury remains unclear. Mitochondrial dysfunction is a key factor in the pathogenesis of ischemic stroke, and impaired mitochondrial function in astrocytes is associated with astrocyte activation. This study aimed to explore the relationship between mitochondrial damage and ischemic stroke and to investigate how ATF3 regulates mitochondrial dysfunction and astrocyte activation in the context of ischemic injury.Methods: In a transient middle cerebral artery occlusion (tMCAO) mouse model, we knocked down ATF3 and assessed infarct size, motor deficits, astrocyte activation, and mitochondrial damage. In vitro, we used oxygen-glucose deprivation and reoxygenation (OGD-R) to simulate ischemia and evaluated the impact of ATF3 knockdown on astrocyte activation and mitochondrial function.Results: ATF3 knockdown exacerbated infarct size, motor deficits, and astrocyte activation in vivo, with increased mitochondrial damage. In vitro, ATF3 depletion worsened mitochondrial dysfunction and astrocyte activation. ATF3 interacted with Drp1 via Akt2, inhibiting mitochondrial fission and protecting astrocytes.Conclusion: ATF3 regulates mitochondrial fission and protects astrocytes in ischemic stroke, highlighting its potential as a therapeutic target for stroke recovery.Keywords: activating transcription factor 3, ATF3, acute ischemic stroke, AIS, astrocytes, mitochondrial dysfunction, dynamics-related protein 1, Drp1, threonine/serine kinase 2, Akt2 |
| format | Article |
| id | doaj-art-c12591dc1e5d4686ac17c13510389a1d |
| institution | Kabale University |
| issn | 1177-5491 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Biologics: Targets & Therapy |
| spelling | doaj-art-c12591dc1e5d4686ac17c13510389a1d2025-02-11T17:30:56ZengDove Medical PressBiologics: Targets & Therapy1177-54912025-02-01Volume 191529100101ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic StrokeHuang RHuang XYang HWu HLiu FSaw PECao MRong Huang,1 Xiaoyan Huang,1 Hongmei Yang,1 Haixuan Wu,1 Fan Liu,1 Phei Er Saw,2,3 Minghui Cao1,4 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 4Department of Anesthesiology, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, People’s Republic of ChinaCorrespondence: Phei Er Saw; Minghui Cao, Email caipeie@mail.sysu.edu.cn; caomh@mail.sysu.edu.cnIntroduction: ATF3, a stress-induced transcription factor, has been implicated in the injury processes of various cell types, including neurons. It is recognized as a common marker for neuronal damage following neurotrauma. However, its role in other types of glial cells, particularly astrocytes, in response to ischemic injury remains unclear. Mitochondrial dysfunction is a key factor in the pathogenesis of ischemic stroke, and impaired mitochondrial function in astrocytes is associated with astrocyte activation. This study aimed to explore the relationship between mitochondrial damage and ischemic stroke and to investigate how ATF3 regulates mitochondrial dysfunction and astrocyte activation in the context of ischemic injury.Methods: In a transient middle cerebral artery occlusion (tMCAO) mouse model, we knocked down ATF3 and assessed infarct size, motor deficits, astrocyte activation, and mitochondrial damage. In vitro, we used oxygen-glucose deprivation and reoxygenation (OGD-R) to simulate ischemia and evaluated the impact of ATF3 knockdown on astrocyte activation and mitochondrial function.Results: ATF3 knockdown exacerbated infarct size, motor deficits, and astrocyte activation in vivo, with increased mitochondrial damage. In vitro, ATF3 depletion worsened mitochondrial dysfunction and astrocyte activation. ATF3 interacted with Drp1 via Akt2, inhibiting mitochondrial fission and protecting astrocytes.Conclusion: ATF3 regulates mitochondrial fission and protects astrocytes in ischemic stroke, highlighting its potential as a therapeutic target for stroke recovery.Keywords: activating transcription factor 3, ATF3, acute ischemic stroke, AIS, astrocytes, mitochondrial dysfunction, dynamics-related protein 1, Drp1, threonine/serine kinase 2, Akt2https://www.dovepress.com/atf3-knockdown-exacerbates-astrocyte-activation-by-inhibiting-phosphor-peer-reviewed-fulltext-article-BTTactivating transcription factor 3 (atf3)acute ischemic stroke (ais)astrocytesmitochondrial dysfunctiondynamics-related protein 1(drp1)threonine/serine kinase 2 (akt2) |
| spellingShingle | Huang R Huang X Yang H Wu H Liu F Saw PE Cao M ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke Biologics: Targets & Therapy activating transcription factor 3 (atf3) acute ischemic stroke (ais) astrocytes mitochondrial dysfunction dynamics-related protein 1(drp1) threonine/serine kinase 2 (akt2) |
| title | ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke |
| title_full | ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke |
| title_fullStr | ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke |
| title_full_unstemmed | ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke |
| title_short | ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke |
| title_sort | atf3 knockdown exacerbates astrocyte activation by inhibiting phosphorylation of drp1 in ischemic stroke |
| topic | activating transcription factor 3 (atf3) acute ischemic stroke (ais) astrocytes mitochondrial dysfunction dynamics-related protein 1(drp1) threonine/serine kinase 2 (akt2) |
| url | https://www.dovepress.com/atf3-knockdown-exacerbates-astrocyte-activation-by-inhibiting-phosphor-peer-reviewed-fulltext-article-BTT |
| work_keys_str_mv | AT huangr atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke AT huangx atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke AT yangh atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke AT wuh atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke AT liuf atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke AT sawpe atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke AT caom atf3knockdownexacerbatesastrocyteactivationbyinhibitingphosphorylationofdrp1inischemicstroke |