AIM To investigate the clinical features ofFADD and TRADD expressions in primaryhepatocellular carcinoma(HCC)and todetermine their relationship with hepaticapoptosis.METHODS FADD and TRADD expressions weredetected by ...AIM To investigate the clinical features ofFADD and TRADD expressions in primaryhepatocellular carcinoma(HCC)and todetermine their relationship with hepaticapoptosis.METHODS FADD and TRADD expressions weredetected by immunohistochemistry and hepaticapoptosis were determined by in situ end-labeling(ISEL).RESULTS Ten(25.6%)cases of HCC weredetected to express FADD protein.The positiverate in HCC is lower than that in non-cancerousadjacent liver tissues(62.5%)(P【0.05).Inthose of grade Ⅰ-Ⅱ,8(38.1%)cases wereFADD positive,while only 2/18(11.1%)casesof grade Ⅲ-Ⅳ had detectable FADD protein(P【0.05).No relationship was found betweenFADD expression and other clinical features,such as gender,age,tumor size,differentiationor metastasis.ISEL positive cells can be seen inall cases of HCC.The hepatic apoptosis wasassociated with FADD expression as moreapoptotic cells were detected in those caseswhich had moderately to strongly positiveFADD,as compared with negative or weakpositive FADD cases(P【0.05).No relationshipwas found between FADD expression and hepaticapoptosis in non-cancerous adjacent livertissues.Fifteen of 39(38.5%)cases of HCCwere found positive for TRADD protein,andsimilar positive rate(37.5%)in non-cancerousadjacent liver tissues(P】0.05).The expressionof TRADD is correlated with HCC differentiation, as only 22.2% of moderately to highlydifferentiated HCC showed positive TRADDprotein,while as high as 52.4% of poorlydifferentiated HCC had TRADD(P【0.05),Norelationship was found between TRADDexpression and gender,age,tumor size or gradeor metastasis,although 42.9% of HCC of gradeⅠ/Ⅱ showed positive TRADD which wasslightly higher than that of grade Ⅲ/Ⅳ(33.3%,P】0.05).Hepatic apoptosis was not related toTRADD expression in HCC or non-cancerousadjacent liver tissues.CONCLUSION Loss of FADD expression playsan important role in HCC carcinogenesis,andexpression of TRADD also contributes to HCCdevelopment.The cell apoptosis in HCC isassociated with FADD expression.However,theexpression of TRADD does not correlate wellwith hepatic apoptosis in HCC.展开更多
TNFR1-associated death domain protein(TRADD)with arginine N-GlcNAcylation is a novel and structurally unique posttranslational modification(PTM)glycoprotein that blocks the formation of death-inducing signaling comple...TNFR1-associated death domain protein(TRADD)with arginine N-GlcNAcylation is a novel and structurally unique posttranslational modification(PTM)glycoprotein that blocks the formation of death-inducing signaling complex(DISC),orchestrating host nuclear factorκB(NF-κB)signaling in entero-pathogenic Escherichia coli(EPEC)-infected cells.This particular glycosylated modification plays an extremely vital role for the effective colonization and pathogenesis of pathogens in the gut.Herein we describe the total synthesis of TRADD death domain(residues 195-312)with arginine235 NGlcNAcylation(Arg-GIcNAc TRADD(195-312)).Two longish peptidyl fragments of the wild-type primary sequence were obtained by robust,microwave-assisted,highly efficient,solid-phase peptide synthesis(SPPS),the N-GlcNAcylated sector was built by total synthesis and attached specifically to resinbound peptide with an unprotected ornithine residue via silver-promoted on-resin guanidinylation,ArgGlcNAc TRADD(195-312)was constructed by hydrazide-based native chemical ligation(NCL).The facile synthetic strategy is expected to be generally applicable for the rapid synthesis of other proteins with Arg-GIcNAc modification and to pave the way for the related chemically biological study.展开更多
Death receptors, including the TNF receptor-1 （TNF-RI）, have been shown to be able to initiate caspase-independent cell death. This form of ＂necrotic cell death＂ appears to be dependent on the generation of reacti...Death receptors, including the TNF receptor-1 （TNF-RI）, have been shown to be able to initiate caspase-independent cell death. This form of ＂necrotic cell death＂ appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNFa and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNFα indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.展开更多
文摘AIM To investigate the clinical features ofFADD and TRADD expressions in primaryhepatocellular carcinoma(HCC)and todetermine their relationship with hepaticapoptosis.METHODS FADD and TRADD expressions weredetected by immunohistochemistry and hepaticapoptosis were determined by in situ end-labeling(ISEL).RESULTS Ten(25.6%)cases of HCC weredetected to express FADD protein.The positiverate in HCC is lower than that in non-cancerousadjacent liver tissues(62.5%)(P【0.05).Inthose of grade Ⅰ-Ⅱ,8(38.1%)cases wereFADD positive,while only 2/18(11.1%)casesof grade Ⅲ-Ⅳ had detectable FADD protein(P【0.05).No relationship was found betweenFADD expression and other clinical features,such as gender,age,tumor size,differentiationor metastasis.ISEL positive cells can be seen inall cases of HCC.The hepatic apoptosis wasassociated with FADD expression as moreapoptotic cells were detected in those caseswhich had moderately to strongly positiveFADD,as compared with negative or weakpositive FADD cases(P【0.05).No relationshipwas found between FADD expression and hepaticapoptosis in non-cancerous adjacent livertissues.Fifteen of 39(38.5%)cases of HCCwere found positive for TRADD protein,andsimilar positive rate(37.5%)in non-cancerousadjacent liver tissues(P】0.05).The expressionof TRADD is correlated with HCC differentiation, as only 22.2% of moderately to highlydifferentiated HCC showed positive TRADDprotein,while as high as 52.4% of poorlydifferentiated HCC had TRADD(P【0.05),Norelationship was found between TRADDexpression and gender,age,tumor size or gradeor metastasis,although 42.9% of HCC of gradeⅠ/Ⅱ showed positive TRADD which wasslightly higher than that of grade Ⅲ/Ⅳ(33.3%,P】0.05).Hepatic apoptosis was not related toTRADD expression in HCC or non-cancerousadjacent liver tissues.CONCLUSION Loss of FADD expression playsan important role in HCC carcinogenesis,andexpression of TRADD also contributes to HCCdevelopment.The cell apoptosis in HCC isassociated with FADD expression.However,theexpression of TRADD does not correlate wellwith hepatic apoptosis in HCC.
基金the National Natural Science Foundation of China (Nos.91849129,21807112)PLA Youth Medical Science and Technology Youth Development Program (No.16QNP086)Foundation of Second Military Medical University (No.2016JS11)
文摘TNFR1-associated death domain protein(TRADD)with arginine N-GlcNAcylation is a novel and structurally unique posttranslational modification(PTM)glycoprotein that blocks the formation of death-inducing signaling complex(DISC),orchestrating host nuclear factorκB(NF-κB)signaling in entero-pathogenic Escherichia coli(EPEC)-infected cells.This particular glycosylated modification plays an extremely vital role for the effective colonization and pathogenesis of pathogens in the gut.Herein we describe the total synthesis of TRADD death domain(residues 195-312)with arginine235 NGlcNAcylation(Arg-GIcNAc TRADD(195-312)).Two longish peptidyl fragments of the wild-type primary sequence were obtained by robust,microwave-assisted,highly efficient,solid-phase peptide synthesis(SPPS),the N-GlcNAcylated sector was built by total synthesis and attached specifically to resinbound peptide with an unprotected ornithine residue via silver-promoted on-resin guanidinylation,ArgGlcNAc TRADD(195-312)was constructed by hydrazide-based native chemical ligation(NCL).The facile synthetic strategy is expected to be generally applicable for the rapid synthesis of other proteins with Arg-GIcNAc modification and to pave the way for the related chemically biological study.
文摘Death receptors, including the TNF receptor-1 （TNF-RI）, have been shown to be able to initiate caspase-independent cell death. This form of ＂necrotic cell death＂ appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNFa and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNFα indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.
