VEGF-mediated NF-κB activation protects PC12 cells from damage induced by hypoxia.


:Neuronal apoptosis is a contributing cause of disability and death in cerebral ischemia. Nuclear factor-κB (NF-κB) may become a potential therapeutic target for hypoxic/ischemic neuron damage because NF-κB is inactivated after hypoxia exposure. Vascular endothelial growth factor (VEGF) has been found to improve neurological function recovery in cerebral ischemic injury although the exact molecular mechanisms that underlie the neuroprotective function of VEGF remain largely unknown. Here we defined the mechanism by which VEGF antagonized neuron-like PC12 cells apoptosis induced by hypoxia mimetic agent cobalt chloride (CoCl2) is through restoration of NF-κB activity. Depletion of VEGF with small interfering RNA (siRNA) in PC12 cells conferred CoCl2-induced cytotoxicity which was mitigated by VEGF administration. Treatment of PC12 cells with VEGF attenuated the CoCl2-induced cytotoxicity in both dose- and time-dependent manner. Mechanistically, VEGF increased IκBα phosphorylation and ubiquitination, promoted P65 nuclear translocation as well as upregulated XIAP and CCND1 expression. Meanwhile, VEGF administration reversed the dysregulation of IκBα phosphorylation and ubiquitination, P65 nuclear translocation as well as XIAP and CCND1 expression induced by CoCl2. Notably, the VEGF-dependent cytoprotection was abolished by pretreatment with BAY 11-7085, a specific inhibitor of NF-κB. Our data suggest that VEGF/NF-κB signalling pathway represents an adaptive mechanism that protects neural cells against hypoxic damage.


Neurosci Lett


Neuroscience letters


Mo SJ,Hong J,Chen X,Han F,Ni Y,Zheng Y,Liu JQ,Xu L,Li Q,Yang XH,Sun RH,Yin XY




Has Abstract


2016-01-01 00:00:00












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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Neuroscience letters

    pub_type: 杂志文章


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    journal_title:Neuroscience letters

    pub_type: 杂志文章


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    journal_title:Neuroscience letters

    pub_type: 杂志文章


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    journal_title:Neuroscience letters

    pub_type: 杂志文章


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