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!
|
| Summary: | 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 [email protected]; [email protected]: 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 |
|---|---|
| ISSN: | 1177-5491 |