Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after middle cerebral artery occlusion in mice.
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.
Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Jianfei
J
Lu
Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Zhao
Z
Jiang
Peking University Center for Human Disease Genomics, Beijing 100191, China.
Yingyu
Y
Chen
Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Changman
C
Zhou
Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: cch@bjmu.edu.cn.
Chunhua
C
Chen
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D002536:Cerebral Arteries / Q000378:metabolism* / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; C486488:Pdcd5 protein, mouse; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C494469:VHL protein, mouse
Apoptosis; Autophagy; Knockout mice; Middle cerebral artery occlusion (MCAO); Programmed cell death 5 (PDCD5)