DUSP1-mediated suppression of p38 MAPK signaling pathway reduces ferroptosis in cerebral ischemia-reperfusion injury
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View abstract on PubMed
Summary
This summary is machine-generated.Dual specificity phosphatase 1 (DUSP1) protects against brain injury after stroke by regulating ferroptosis. DUSP1 overexpression reduces ferroptosis and brain damage, while its inhibition worsens outcomes.
Area Of Science
- Neuroscience
- Cell Biology
- Biochemistry
Background
- Ferroptosis is a key factor in cerebral ischemia-reperfusion injury (CI/RI), impacting neurological function.
- Dual specificity phosphatase 1 (DUSP1) shows neuroprotective potential, but its role in ferroptosis is unclear.
Purpose Of The Study
- To investigate DUSP1's therapeutic potential by examining its role in ferroptosis modulation in cerebral ischemia-reperfusion injury.
- To elucidate the mechanism of DUSP1's neuroprotection via ferroptosis regulation.
Main Methods
- In vitro: PC12 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) with DUSP1 manipulation (overexpression/knockdown).
- In vivo: Middle cerebral artery occlusion/reperfusion (MCAO/R) rat models with DUSP1 pharmacological inhibition.
- Assessed ferroptosis markers, cell viability, infarction volume, neurological deficits, and histopathology.
- Investigated the involvement of the p38 mitogen-activated protein kinase pathway.
Main Results
- Ferroptosis was induced in OGD/R and MCAO/R models, correlating with increased DUSP1 expression.
- DUSP1 overexpression attenuated ferroptosis and CI/RI, while knockdown worsened injury.
- DUSP1 inhibition aggravated cerebral injury and ferroptosis markers in MCAO/R rats.
- Adezipimod treatment rescued ferroptosis in DUSP1-deficient cells by modulating key ferroptosis-related proteins.
Conclusions
- DUSP1 confers neuroprotection against CI/RI by regulating ferroptosis via the p38 pathway.
- DUSP1 represents a promising therapeutic target for ischemic stroke treatment.
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