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Updated: Mar 15, 2026
Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after middle cerebral artery occlusion in
Jianfei Lu1, Zhao Jiang1, Yingyu Chen2
1Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Abstract:
Loss of von Hippel-Lindau tumor suppressor protein (VHL) or hypoxia results in nuclear relocalization of PDCD5 and subsequent mouse double minute 2 homolog (Mdm2) degradation. Thus, VHL may involved in the PDCD5 mediated apoptosis and autophagy after MCAO. In the present study, using PDCD5 knockout (PDCD5-/-) mice, we aimed to demonstrate that knockout of PDCD5 gene could protect the brain from ischemic injury by inhibiting the PDCD5-VHL pathway. 24h post MCAO surgery, PDCD5 gene knockout mice presented obvious improved brain blood flow, improved neurological behavior and decreased cerebral infarction compared with wild type mice. The levels of apoptotic and autophagic proteins were increased both in wild type and PDCD5 knockout mice, whereas they were more pronounced in the wild type mice. We observed decrease in the expression of VHL in wild type mice after MCAO. Reduced expression of VHL may result in increased expression of hypoxia-inducible factor 1α(HIF-1α) and (BCL2/adenovirus E1B 19kDa protein-interacting protein 3) BNIP3. However, mice lacking PDCD5 had no changes in the expression of VHL and have slighter increases in the expression of HIF-1α and BNIP3, suggesting that PDCD5 may regulate apoptosis and autophagy through VHL-HIF-1α-BNIP3 pathway.
Insights
PDCD5 gene knockout protects the brain from ischemic injury by modulating the PDCD5-VHL pathway. This study reveals PDCD5 regulates apoptosis and autophagy via the VHL-HIF-1α-BNIP3 pathway, offering neuroprotective insights.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Biology
Background:
- Loss of the von Hippel-Lindau tumor suppressor protein (VHL) or hypoxia induces PDCD5 nuclear relocalization and Mdm2 degradation.
- VHL may play a role in PDCD5-mediated apoptosis and autophagy following MCAO.
Purpose of the Study:
- To investigate if PDCD5 gene knockout protects the brain from ischemic injury by inhibiting the PDCD5-VHL pathway.
- To elucidate the role of PDCD5 in regulating apoptosis and autophagy post-MCAO.
Main Methods:
- Utilized PDCD5 knockout (PDCD5-/-) mice and wild-type littermates.
- Performed MCAO surgery to induce ischemic stroke.
- Assessed brain blood flow, neurological behavior, cerebral infarction, and protein expression levels.
Main Results:
- PDCD5 knockout mice showed improved brain blood flow, neurological function, and reduced cerebral infarction 24 hours post-MCAO.
- While both groups exhibited increased apoptotic and autophagic proteins, wild-type mice showed more pronounced increases.
- PDCD5 knockout prevented VHL downregulation and attenuated the upregulation of HIF-1α and BNIP3 observed in wild-type mice post-MCAO.
Conclusions:
- PDCD5 knockout confers neuroprotection against ischemic injury.
- PDCD5 regulates apoptosis and autophagy, potentially through the VHL-HIF-1α-BNIP3 pathway.
