Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believ...Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believed that this sensitization is due to the transcriptional blockade of genes regulated by NF-κB. Nevertheless, such evidence has remained elusive in the nervous system. Here, we show that TNF-α cannot normally induce apoptosis in PC12 cells or cortical neurons. However, cells treated with Actinomycin D (ActD) become susceptible to TNF-α-induced cell death through the activation of caspase-8, generation of tBid and activation of caspase-9 and -3. Analysis of several proteins involved in TNF-α receptor signaling showed no significant downregulation of NF-κB target genes, such as IAPs or FLIP, under such conditions. However, Bcl-XL protein levels, but not those of Bcl-2, Bax and Bak, are reduced by ActD or TNF-α/ ActD treatments. Moreover, Bcl-xL overexpression fully protects cells against TNF-α/ActD-induced cell death. When endogenous levels of Bcl-XL are specifically downregulated by lentiviral-based RNAi, cells no longer require ActD to be sensitive to TNF-α-triggered apoptosis. Furthermore, Bcl-xL downregulation does not affect TNF-α-mediated NF-κB activation. Altogether, our results demonstrate that Bcl-XL, and not Bci-2, FLIP or IAPs, acts as the endogenous regulator of neuronal resistance/sensitivity to TNF-α-induced apoptosis in an NF-κB-independent manner.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal copublished by EWA Publishing and Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engin...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal copublished by EWA Publishing and Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA ...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal copublished by EWA Publishing and Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engin...Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal copublished by EWA Publishing and Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.展开更多
文摘Upon activation, tumor necrosis factor alpha (TNF-α) receptor can engage apoptotic or survival pathways. Inhibition of macromolecular synthesis is known to sensitize cells to TNF-α-induced cell death. It is believed that this sensitization is due to the transcriptional blockade of genes regulated by NF-κB. Nevertheless, such evidence has remained elusive in the nervous system. Here, we show that TNF-α cannot normally induce apoptosis in PC12 cells or cortical neurons. However, cells treated with Actinomycin D (ActD) become susceptible to TNF-α-induced cell death through the activation of caspase-8, generation of tBid and activation of caspase-9 and -3. Analysis of several proteins involved in TNF-α receptor signaling showed no significant downregulation of NF-κB target genes, such as IAPs or FLIP, under such conditions. However, Bcl-XL protein levels, but not those of Bcl-2, Bax and Bak, are reduced by ActD or TNF-α/ ActD treatments. Moreover, Bcl-xL overexpression fully protects cells against TNF-α/ActD-induced cell death. When endogenous levels of Bcl-XL are specifically downregulated by lentiviral-based RNAi, cells no longer require ActD to be sensitive to TNF-α-triggered apoptosis. Furthermore, Bcl-xL downregulation does not affect TNF-α-mediated NF-κB activation. Altogether, our results demonstrate that Bcl-XL, and not Bci-2, FLIP or IAPs, acts as the endogenous regulator of neuronal resistance/sensitivity to TNF-α-induced apoptosis in an NF-κB-independent manner.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal copublished by EWA Publishing and Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal hosted by Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering,published by EWA Publishing.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.
文摘Advances in Engineering Innovation(AEI)is a peer-reviewed,fast-indexing open access journal copublished by EWA Publishing and Tianjin University Research Centre on Data Intelligence and Cloud-Edge-Client Service Engineering.AEI is a comprehensive journal focusing on multidisciplinary areas of engineering and at the interface of related subjects,including,but not limited to,Artificial Intelligence,Biomedical Engineering,Electrical and Electronic Engineering,Materials Engineering,Traffic and Transportation Engineering,etc.