The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Mack H Wu - One of the best experts on this subject based on the ideXlab platform.
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targeting Palmitoyl Acyltransferase zdhhc21 improves gut epithelial barrier dysfunction resulting from burn induced systemic inflammation
American Journal of Physiology-gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) medi...
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Targeting Palmitoyl Acyltransferase ZDHHC21 Improves Gut Epithelial Barrier Dysfunction Resulting from Burn Induced Systemic Inflammation
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular Palmitoyl Acyltransferase, zinc finger DHHC domaincontaining protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Using quantitative PCR, we show that ZDHHC21 mRNA production was enhanced twofold when intestinal epithelial cells were treated with TNF-alpha-IFN-gamma in vitro. In addition, pharmacological targeting of Palmitoyl Acyltransferases with 2-bromopalmitate (2-BP) showed significant improvement in TNF-alpha-IFN-gamma-mediated epithelial barrier dysfunction by using electric cell-substrate impedance-sensing assays, as well as FITC-labeled dextran permeability assays. Using acylbiotin exchange assay and click chemistry, we show that TNF-alpha-IFN-gamma treatment of intestinal epithelial cells results in enhanced detection of total Palmitoylated proteins and this response is inhibited by 2-BP. Using ZDHHC21-deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, hematoxylin and eosin staining of the small intestine, as well as transmission electron microscopy, showed that mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury-induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. NEW & NOTEWORTHY Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) mediates gut epithelial hyperpermeability resulting from an experimental model of thermal injury. The hyperpermeability response was significantly attenuated with a pharmacological inhibitor of Palmitoyl Acyltransferases and in mice with genetic ablation of ZDHHC21. These findings suggest that ZDHHC21 may serve as a novel therapeutic target for treating burn-induced intestinal barrier dysfunction.Copyright © 2017 the American Physiological Society.
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Palmitoyl Acyltransferase dhhc21 mediates endothelial dysfunction in systemic inflammatory response syndrome
Nature Communications, 2016Co-Authors: Richard S Beard, Clement Gy Yang, Xiaoyuan Yang, Jamie E Meegan, Jonathan W Overstreet, John A Elliott, Jason J Reynolds, Christopher D Pivetti, David A Mitchell, Mack H WuAbstract:Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that Palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of Palmitoyl Acyltransferase DHHC21 as potential disease therapy.
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Palmitoyl Acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome
Nature Communications, 2016Co-Authors: Richard S Beard, Clement Gy Yang, Xiaoyuan Yang, Jamie E Meegan, Jonathan W Overstreet, John A Elliott, Jason J Reynolds, Christopher D Pivetti, David A Mitchell, Mack H WuAbstract:Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that Palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of Palmitoyl Acyltransferase DHHC21 as potential disease therapy. Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing Palmitoyl Acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency ( Zdhhc21 ^ dep/dep ) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21 ^ dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCβ1 Palmitoylation and signalling activity, effects significantly reduced in Zdhhc21 ^ dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCβ1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCβ1 Palmitoylation in endothelial inflammation.
Clement Gy Yang - One of the best experts on this subject based on the ideXlab platform.
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targeting Palmitoyl Acyltransferase zdhhc21 improves gut epithelial barrier dysfunction resulting from burn induced systemic inflammation
American Journal of Physiology-gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) medi...
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Targeting Palmitoyl Acyltransferase ZDHHC21 Improves Gut Epithelial Barrier Dysfunction Resulting from Burn Induced Systemic Inflammation
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular Palmitoyl Acyltransferase, zinc finger DHHC domaincontaining protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Using quantitative PCR, we show that ZDHHC21 mRNA production was enhanced twofold when intestinal epithelial cells were treated with TNF-alpha-IFN-gamma in vitro. In addition, pharmacological targeting of Palmitoyl Acyltransferases with 2-bromopalmitate (2-BP) showed significant improvement in TNF-alpha-IFN-gamma-mediated epithelial barrier dysfunction by using electric cell-substrate impedance-sensing assays, as well as FITC-labeled dextran permeability assays. Using acylbiotin exchange assay and click chemistry, we show that TNF-alpha-IFN-gamma treatment of intestinal epithelial cells results in enhanced detection of total Palmitoylated proteins and this response is inhibited by 2-BP. Using ZDHHC21-deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, hematoxylin and eosin staining of the small intestine, as well as transmission electron microscopy, showed that mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury-induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. NEW & NOTEWORTHY Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) mediates gut epithelial hyperpermeability resulting from an experimental model of thermal injury. The hyperpermeability response was significantly attenuated with a pharmacological inhibitor of Palmitoyl Acyltransferases and in mice with genetic ablation of ZDHHC21. These findings suggest that ZDHHC21 may serve as a novel therapeutic target for treating burn-induced intestinal barrier dysfunction.Copyright © 2017 the American Physiological Society.
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Palmitoyl Acyltransferase dhhc21 mediates endothelial dysfunction in systemic inflammatory response syndrome
Nature Communications, 2016Co-Authors: Richard S Beard, Clement Gy Yang, Xiaoyuan Yang, Jamie E Meegan, Jonathan W Overstreet, John A Elliott, Jason J Reynolds, Christopher D Pivetti, David A Mitchell, Mack H WuAbstract:Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that Palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of Palmitoyl Acyltransferase DHHC21 as potential disease therapy.
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Palmitoyl Acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome
Nature Communications, 2016Co-Authors: Richard S Beard, Clement Gy Yang, Xiaoyuan Yang, Jamie E Meegan, Jonathan W Overstreet, John A Elliott, Jason J Reynolds, Christopher D Pivetti, David A Mitchell, Mack H WuAbstract:Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that Palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of Palmitoyl Acyltransferase DHHC21 as potential disease therapy. Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing Palmitoyl Acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency ( Zdhhc21 ^ dep/dep ) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21 ^ dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCβ1 Palmitoylation and signalling activity, effects significantly reduced in Zdhhc21 ^ dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCβ1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCβ1 Palmitoylation in endothelial inflammation.
Russell J. Haines - One of the best experts on this subject based on the ideXlab platform.
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targeting Palmitoyl Acyltransferase zdhhc21 improves gut epithelial barrier dysfunction resulting from burn induced systemic inflammation
American Journal of Physiology-gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) medi...
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Targeting Palmitoyl Acyltransferase ZDHHC21 Improves Gut Epithelial Barrier Dysfunction Resulting from Burn Induced Systemic Inflammation
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular Palmitoyl Acyltransferase, zinc finger DHHC domaincontaining protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Using quantitative PCR, we show that ZDHHC21 mRNA production was enhanced twofold when intestinal epithelial cells were treated with TNF-alpha-IFN-gamma in vitro. In addition, pharmacological targeting of Palmitoyl Acyltransferases with 2-bromopalmitate (2-BP) showed significant improvement in TNF-alpha-IFN-gamma-mediated epithelial barrier dysfunction by using electric cell-substrate impedance-sensing assays, as well as FITC-labeled dextran permeability assays. Using acylbiotin exchange assay and click chemistry, we show that TNF-alpha-IFN-gamma treatment of intestinal epithelial cells results in enhanced detection of total Palmitoylated proteins and this response is inhibited by 2-BP. Using ZDHHC21-deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, hematoxylin and eosin staining of the small intestine, as well as transmission electron microscopy, showed that mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury-induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. NEW & NOTEWORTHY Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) mediates gut epithelial hyperpermeability resulting from an experimental model of thermal injury. The hyperpermeability response was significantly attenuated with a pharmacological inhibitor of Palmitoyl Acyltransferases and in mice with genetic ablation of ZDHHC21. These findings suggest that ZDHHC21 may serve as a novel therapeutic target for treating burn-induced intestinal barrier dysfunction.Copyright © 2017 the American Physiological Society.
Rebecca A Eitnier - One of the best experts on this subject based on the ideXlab platform.
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targeting Palmitoyl Acyltransferase zdhhc21 improves gut epithelial barrier dysfunction resulting from burn induced systemic inflammation
American Journal of Physiology-gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) medi...
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Targeting Palmitoyl Acyltransferase ZDHHC21 Improves Gut Epithelial Barrier Dysfunction Resulting from Burn Induced Systemic Inflammation
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular Palmitoyl Acyltransferase, zinc finger DHHC domaincontaining protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Using quantitative PCR, we show that ZDHHC21 mRNA production was enhanced twofold when intestinal epithelial cells were treated with TNF-alpha-IFN-gamma in vitro. In addition, pharmacological targeting of Palmitoyl Acyltransferases with 2-bromopalmitate (2-BP) showed significant improvement in TNF-alpha-IFN-gamma-mediated epithelial barrier dysfunction by using electric cell-substrate impedance-sensing assays, as well as FITC-labeled dextran permeability assays. Using acylbiotin exchange assay and click chemistry, we show that TNF-alpha-IFN-gamma treatment of intestinal epithelial cells results in enhanced detection of total Palmitoylated proteins and this response is inhibited by 2-BP. Using ZDHHC21-deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, hematoxylin and eosin staining of the small intestine, as well as transmission electron microscopy, showed that mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury-induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. NEW & NOTEWORTHY Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) mediates gut epithelial hyperpermeability resulting from an experimental model of thermal injury. The hyperpermeability response was significantly attenuated with a pharmacological inhibitor of Palmitoyl Acyltransferases and in mice with genetic ablation of ZDHHC21. These findings suggest that ZDHHC21 may serve as a novel therapeutic target for treating burn-induced intestinal barrier dysfunction.Copyright © 2017 the American Physiological Society.
Chunyan Wang - One of the best experts on this subject based on the ideXlab platform.
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targeting Palmitoyl Acyltransferase zdhhc21 improves gut epithelial barrier dysfunction resulting from burn induced systemic inflammation
American Journal of Physiology-gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) medi...
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Targeting Palmitoyl Acyltransferase ZDHHC21 Improves Gut Epithelial Barrier Dysfunction Resulting from Burn Induced Systemic Inflammation
American Journal of Physiology - Gastrointestinal and Liver Physiology, 2017Co-Authors: Russell J. Haines, Clement Gy Yang, Rebecca A Eitnier, Chunyan Wang, Fang Wang, Mack H WuAbstract:Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular Palmitoyl Acyltransferase, zinc finger DHHC domaincontaining protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Using quantitative PCR, we show that ZDHHC21 mRNA production was enhanced twofold when intestinal epithelial cells were treated with TNF-alpha-IFN-gamma in vitro. In addition, pharmacological targeting of Palmitoyl Acyltransferases with 2-bromopalmitate (2-BP) showed significant improvement in TNF-alpha-IFN-gamma-mediated epithelial barrier dysfunction by using electric cell-substrate impedance-sensing assays, as well as FITC-labeled dextran permeability assays. Using acylbiotin exchange assay and click chemistry, we show that TNF-alpha-IFN-gamma treatment of intestinal epithelial cells results in enhanced detection of total Palmitoylated proteins and this response is inhibited by 2-BP. Using ZDHHC21-deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, hematoxylin and eosin staining of the small intestine, as well as transmission electron microscopy, showed that mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury-induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. NEW & NOTEWORTHY Increased mucosal permeability in the gut is one of the major complications following severe burn. Here we report the novel finding that zinc finger DHHC domain-containing protein-21 (ZDHHC21) mediates gut epithelial hyperpermeability resulting from an experimental model of thermal injury. The hyperpermeability response was significantly attenuated with a pharmacological inhibitor of Palmitoyl Acyltransferases and in mice with genetic ablation of ZDHHC21. These findings suggest that ZDHHC21 may serve as a novel therapeutic target for treating burn-induced intestinal barrier dysfunction.Copyright © 2017 the American Physiological Society.
