The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Xiangguo Liu - One of the best experts on this subject based on the ideXlab platform.
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pkcδ regulates death receptor 5 expression induced by ps 341 through atf4 atf3 chop axis in human lung cancer cells
Molecular Cancer Therapeutics, 2012Co-Authors: Xiangguo LiuAbstract:PS-341 (bortezomib), a proteasome inhibitor, has been approved for the treatment of multiple myeloma. Our previous work has shown that PS-341 induces death receptor 5 (DR5)–dependent apoptosis and enhances the TNF-related apoptosis-inducing ligand–induced apoptosis in human non–small cell lung cancer cells. However, the definite mechanism remains undefined. In the present study, we reveal that PKCδ and RSK2 mediate PS-341–induced DR5 Upregulation, involving coactivation of endoplasmic reticulum (ER) stress. We discovered that PS-341 activated ER stress through elevating the expression of BiP, p-eIF2α, IRE1α, ATF4, ATF3, and CCAAT/enhancer-binding protein homologous protein (CHOP). Further study showed that DR5 Upregulation was dependent on ATF4, ATF3, and CHOP expression. Silencing either one of the ATF4, ATF3, and CHOP expression decreased DR5 Upregulation and subsequent apoptosis. We determined that ATF4 regulated ATF3 and CHOP expression. Thereafter, ATF3 and CHOP formed a complex and regulated DR5 expression. In addition, we discovered that the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and RSK2 were elevated after PS-341 treatment and inhibition of their phosphorylation using MAP-ERK kinase 1/2 inhibitor decreased the DR5 level, indicating that ERK/RSK2 signaling is involved in DR5 Upregulation. Furthermore, we detected the cleavage of PKCδ, and the blockage of PKCδ expression cut down DR5 Upregulation and apoptosis. Importantly, knockdown of PKCδ expression decreased the induction of ER stress and the phosphorylation of ERK1/2 and RSK2, suggesting that PKCδ regulates DR5 expression through ERK/RSK2 signaling and ATF4–CHOP/ATF3 axis. Collectively, we show that PS-341 induces PKCδ-dependent DR5 expression through activation of ERK/RSK2 and ER stress signaling pathway. Mol Cancer Ther; 11(10); 2174–82. ©2012 AACR .
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pkcδ regulates death receptor 5 expression induced by ps 341 through atf4 atf3 chop axis in human lung cancer cells
Molecular Cancer Therapeutics, 2012Co-Authors: Xiangguo LiuAbstract:PS-341 (bortezomib), a proteasome inhibitor, has been approved for the treatment of multiple myeloma. Our previous work has shown that PS-341 induces death receptor 5 (DR5)-dependent apoptosis and enhances the TNF-related apoptosis-inducing ligand-induced apoptosis in human non-small cell lung cancer cells. However, the definite mechanism remains undefined. In the present study, we reveal that PKCδ and RSK2 mediate PS-341-induced DR5 Upregulation, involving coactivation of endoplasmic reticulum (ER) stress. We discovered that PS-341 activated ER stress through elevating the expression of BiP, p-eIF2α, IRE1α, ATF4, ATF3, and CCAAT/enhancer-binding protein homologous protein (CHOP). Further study showed that DR5 Upregulation was dependent on ATF4, ATF3, and CHOP expression. Silencing either one of the ATF4, ATF3, and CHOP expression decreased DR5 Upregulation and subsequent apoptosis. We determined that ATF4 regulated ATF3 and CHOP expression. Thereafter, ATF3 and CHOP formed a complex and regulated DR5 expression. In addition, we discovered that the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and RSK2 were elevated after PS-341 treatment and inhibition of their phosphorylation using MAP-ERK kinase 1/2 inhibitor decreased the DR5 level, indicating that ERK/RSK2 signaling is involved in DR5 Upregulation. Furthermore, we detected the cleavage of PKCδ, and the blockage of PKCδ expression cut down DR5 Upregulation and apoptosis. Importantly, knockdown of PKCδ expression decreased the induction of ER stress and the phosphorylation of ERK1/2 and RSK2, suggesting that PKCδ regulates DR5 expression through ERK/RSK2 signaling and ATF4-CHOP/ATF3 axis. Collectively, we show that PS-341 induces PKCδ-dependent DR5 expression through activation of ERK/RSK2 and ER stress signaling pathway.
Camillo Ricordi - One of the best experts on this subject based on the ideXlab platform.
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heme oxygenase 1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation
Diabetes, 2001Co-Authors: Antonello Pileggi, Damaris R Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher A Fraker, Camillo RicordiAbstract:Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 Upregulation in a β-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 Upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 Upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 Upregulation might result in improved success in islet transplantation.
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heme oxygenase 1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation
Diabetes, 2001Co-Authors: Antonello Pileggi, Damaris R Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher A Fraker, Camillo RicordiAbstract:Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 Upregulation in a beta-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 Upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 Upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 Upregulation might result in improved success in islet transplantation.
Caterina Vizzardelli - One of the best experts on this subject based on the ideXlab platform.
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heme oxygenase 1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation
Diabetes, 2001Co-Authors: Antonello Pileggi, Damaris R Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher A Fraker, Camillo RicordiAbstract:Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 Upregulation in a β-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 Upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 Upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 Upregulation might result in improved success in islet transplantation.
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heme oxygenase 1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation
Diabetes, 2001Co-Authors: Antonello Pileggi, Damaris R Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher A Fraker, Camillo RicordiAbstract:Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 Upregulation in a beta-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 Upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 Upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 Upregulation might result in improved success in islet transplantation.
Pierre Cattan - One of the best experts on this subject based on the ideXlab platform.
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heme oxygenase 1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation
Diabetes, 2001Co-Authors: Antonello Pileggi, Damaris R Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher A Fraker, Camillo RicordiAbstract:Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 Upregulation in a β-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 Upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 Upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 Upregulation might result in improved success in islet transplantation.
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heme oxygenase 1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation
Diabetes, 2001Co-Authors: Antonello Pileggi, Damaris R Molano, Thierry Berney, Pierre Cattan, Caterina Vizzardelli, Robert Oliver, Christopher A Fraker, Camillo RicordiAbstract:Transplantation of islets of Langerhans represents a viable therapeutic approach for the treatment of type 1 diabetes. Unfortunately, transplanted islets are susceptible to allogeneic recognition and rejection, recurrence of autoimmunity, and destruction by local inflammation at the site of implantation. The last of these phenomena might not only result in functional impairment and death of islet cells but could also contribute to amplifying the subsequent specific immune response. Induction of islet cell protection against inflammation could therefore be postulated to be a powerful means to improve overall graft fate. Heme oxygenase-1 (HO-1) has been described as an inducible protein capable of cytoprotection via radical scavenging and apoptosis prevention. The purpose of the present study was to analyze whether HO-1 Upregulation in a beta-cell line and in freshly isolated murine islets could result in protection from apoptosis and improve in vivo functional performance. HO-1 Upregulation was induced reproducibly with protoporphyrins and was correlated with protection from apoptosis induced in vitro with proinflammatory cytokines or Fas engagement. Furthermore, in vivo HO-1 Upregulation resulted in improved islet function in a model of marginal mass islet transplantation in rodents. Strategies aimed at inducing HO-1 Upregulation might result in improved success in islet transplantation.
Melitta Schachner - One of the best experts on this subject based on the ideXlab platform.
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the asparaginyl endopeptidase legumain is essential for functional recovery after spinal cord injury in adult zebrafish
PLOS ONE, 2014Co-Authors: Yanqin Shen, Harsh P Khatri, Melitta SchachnerAbstract:Unlike mammals, adult zebrafish are capable of regenerating severed axons and regaining locomotor function after spinal cord injury. A key factor for this regenerative capacity is the innate ability of neurons to re-express growth-associated genes and regrow their axons after injury in a permissive environment. By microarray analysis, we have previously shown that the expression of legumain (also known as asparaginyl endopeptidase) is upregulated after complete transection of the spinal cord. In situ hybridization showed Upregulation of legumain expression in neurons of regenerative nuclei during the phase of axon regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein expression was confirmed by immunohistochemistry. Interestingly, Upregulation of legumain expression was also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury. The role of legumain in locomotor function after spinal cord injury was tested by reducing Legumain expression by application of anti-sense morpholino oligonucleotides. Using two independent anti-sense morpholinos, locomotor recovery and axonal regrowth were impaired when compared with a standard control morpholino. We conclude that Upregulation of legumain expression after spinal cord injury in the adult zebrafish is an essential component of the capacity of injured neurons to regrow their axons. Another feature contributing to functional recovery implicates Upregulation of legumain expression in the spinal cord caudal to the injury site. In conclusion, we established for the first time a function for an unusual protease, the asparaginyl endopeptidase, in the nervous system. This study is also the first to demonstrate the importance of legumain for repair of an injured adult central nervous system of a spontaneously regenerating vertebrate and is expected to yield insights into its potential in nervous system regeneration in mammals.
