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Pesquisa : D08.811.277.656.262.500.126.550.800 [Categoria DeCS]
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[PMID]:28462525
[Au] Autor:Tummers B; Green DR
[Ad] Endereço:Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
[Ti] Título:Caspase-8: regulating life and death.
[So] Source:Immunol Rev;277(1):76-89, 2017 05.
[Is] ISSN:1600-065X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be triggered to engage molecular programs that result in cell death. Such triggers include cellular stress, oncogenic signals that engage tumor suppressor mechanisms, pathogen insults, and immune mechanisms. The best-known forms of programmed cell death are apoptosis and a recently recognized regulated necrosis termed necroptosis. Of the two best understood pathways of apoptosis, the extrinsic and intrinsic (mitochondrial) pathways, the former is induced by the ligation of death receptors, a subset of the TNF receptor (TNFR) superfamily. Ligation of these death receptors can also induce necroptosis. The extrinsic apoptosis and necroptosis pathways regulate each other and their balance determines whether cells live. Integral in the regulation and initiation of death receptor-mediated activation of programmed cell death is the aspartate-specific cysteine protease (caspase)-8. This review describes the role of caspase-8 in the initiation of extrinsic apoptosis execution and the mechanism by which caspase-8 inhibits necroptosis. The importance of caspase-8 in the development and homeostasis and the way that dysfunctional caspase-8 may contribute to the development of malignancies in mice and humans are also explored.
[Mh] Termos MeSH primário: Caspase 8/imunologia
Inflamassomos/metabolismo
Mitocôndrias/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose
Homeostase
Seres Humanos
Necrose
Receptores de Morte Celular/metabolismo
Receptores do Fator de Necrose Tumoral/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Inflammasomes); 0 (Receptors, Death Domain); 0 (Receptors, Tumor Necrosis Factor); 0 (Tumor Necrosis Factor-alpha); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1111/imr.12541


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[PMID]:28460471
[Au] Autor:Zhao L; Yang G; Bai H; Zhang M; Mou D
[Ad] Endereço:Department of General Surgery, The First Hospital of Tsinghua University, Beijing, China.
[Ti] Título:NCTD promotes Birinapant-mediated anticancer activity in breast cancer cells by downregulation of c-FLIP.
[So] Source:Oncotarget;8(16):26886-26895, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Second mitochondria-derived activator of caspases (SMAC) mimetics is a class of new anticancer agents. However, most cancers exhibit de novo or acquired resistance to SMAC mimetics, posting a problem for broad applications in clinic, and highlighting the necessity of exploring combinational strategies to circumvent SMAC mimetic-resistance. We here showed that Norcantharidin, a drug that is currently being used in cancer treatment, significantly enhanced SMAC mimetic Birinapant-mediated cell viability inhibition and robustly promoted apoptosis in established breast carcinoma cell lines, as well as in primary breast carcinoma cells. Mechanistically, we revealed that Norcantharidin effectively reduced the levels of two major protein isoforms of cellular FLICE-like inhibitor protein(c-FLIP), namely c-FLIP long (c-FLIPL) and c-FLIP short (c-FLIPS). Moreover, Norcantharidin markedly enhanced Birinapant-triggered caspase-8/caspase-3 cascade. Inhibition of caspase-8 activity by a synthetic peptide Z-IETD-FMK significantly attenuated cell death induction by the combination, suggesting that caspase-8 plays a critical role in the anticancer action. In conclusion, our study suggests that the combination of SMAC mimetics with Norcantharidin represents a novel strategy in breast cancer therapy and warrants further studies.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Neoplasias da Mama/genética
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética
Dipeptídeos/farmacologia
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Indóis/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Caspase 8/metabolismo
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Feminino
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (CASP8 and FADD-Like Apoptosis Regulating Protein); 0 (Dipeptides); 0 (Indoles); 6O4Z07B57R (birinapant); 8452E71EO7 (norcantharidin); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15848


  3 / 5262 MEDLINE  
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[PMID]:28453927
[Au] Autor:Gentle IE; McHenry KT; Weber A; Metz A; Kretz O; Porter D; Häcker G
[Ad] Endereço:Faculty of Medicine, Institute for Medical Microbiology and Hygiene, Medical Center - University of Freiburg, University of Freiburg, Germany.
[Ti] Título:TIR-domain-containing adapter-inducing interferon-ß (TRIF) forms filamentous structures, whose pro-apoptotic signalling is terminated by autophagy.
[So] Source:FEBS J;284(13):1987-2003, 2017 07.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The formation of amyloid-like protein structures has recently emerged as a feature in signal transduction, particularly in innate immunity. These structures appear to depend on defined domains for their formation but likely also require dedicated ways to terminate signalling. We, here, define the innate immunity protein/Toll-like receptor adaptor TIR-domain-containing adapter-inducing interferon-ß (TRIF) as a novel platform of fibril formation and probe signal initiation through TRIF as well as its termination in Toll-like receptor 3 (TLR3)-stimulated melanoma cells. A main signalling pathway triggered by TLR3 caused apoptosis, which was controlled by inhibitor of apoptosis proteins and was dependent on RIPK1 and independent of TNF. Using correlative electron/fluorescence microscopy, we visualised fibrillar structures formed through both Toll/interleukin-1 receptor and RIP homotypic interacting motif regions of TRIF. We provide evidence that these fibrillary structures are active signalling platforms whose activity is terminated by autophagy. TRIF-signalling enhanced autophagy, and fibrillary structures were partly contained within autophagosomes. Inhibition of autophagy increased levels of pro-apoptotic TRIF complexes, leading to the accumulation of active caspase-8 and enhanced apoptosis while stimulation of autophagy reduced TRIF-dependent death. We conclude that pro-death signals through TRIF are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transporte Vesicular/metabolismo
Apoptose/fisiologia
Autofagia/fisiologia
Transdução de Sinais
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transporte Vesicular/química
Proteínas Adaptadoras de Transporte Vesicular/genética
Animais
Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Western Blotting
Caspase 8/genética
Caspase 8/metabolismo
Linhagem Celular Tumoral
Células Cultivadas
Células HEK293
Células HeLa
Seres Humanos
Camundongos Knockout
Microscopia Eletrônica de Transmissão
Microscopia de Fluorescência
Oligopeptídeos/farmacologia
Poli I-C/farmacologia
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Receptor 3 Toll-Like/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Vesicular Transport); 0 (LBW242); 0 (Oligopeptides); 0 (TICAM1 protein, human); 0 (Toll-Like Receptor 3); EC 2.7.11.1 (RIPK1 protein, human); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 3.4.22.- (Caspase 8); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14091


  4 / 5262 MEDLINE  
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[PMID]:29330116
[Au] Autor:Wen SH; Lin LN; Wu HJ; Yu L; Lin L; Zhu LL; Li HY; Zhang HL; Li CC
[Ad] Endereço:Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, PR China.
[Ti] Título:TNF-α increases Staphylococcus aureus-induced death of human alveolar epithelial cell line A549 associated with RIP3-mediated necroptosis.
[So] Source:Life Sci;195:81-86, 2018 Feb 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIM: To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN METHODS: The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus, where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were analyzed by western blot. KEY FINDINGS: S. aureus-induced LDH release was increased significantly by TNF-α. In addition, flow cytometry showed that TNF-α increased A549 cell apoptosis and necrosis in S. aureus-infected cell cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected with S. aureus increased at 12 h post-infection, as shown by western blot. Significant additional increases in RIP3 expression were observed following the addition of TNF-α. Decreasing RIP3 levels by siRNA significantly suppressed the release of LDH induced by TNF-α and S. aureus. RIP3 siRNA also significantly suppressed A549 cell necrosis induced by S. aureus and TNF-α at 6 and 12 h post-infection as shown by flow cytometry analysis. SIGNIFICANCE: TNF-α enhances the damage of S. aureus on lung epithelial cells, and its mechanism is associated with RIP3 mediated necroptosis.
[Mh] Termos MeSH primário: Morte Celular/efeitos dos fármacos
Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia
Staphylococcus aureus/efeitos dos fármacos
Fator de Necrose Tumoral alfa/farmacologia
[Mh] Termos MeSH secundário: Células A549
Células Epiteliais Alveolares
Caspase 8/genética
Caspase 8/metabolismo
Seres Humanos
L-Lactato Desidrogenase/metabolismo
Necrose/induzido quimicamente
Necrose/patologia
Complexo de Proteínas Formadoras de Poros Nucleares/efeitos dos fármacos
Complexo de Proteínas Formadoras de Poros Nucleares/fisiologia
Proteínas de Ligação a RNA/efeitos dos fármacos
Proteínas de Ligação a RNA/fisiologia
Proteína Serina-Treonina Quinases de Interação com Receptores/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AGFG1 protein, human); 0 (Nuclear Pore Complex Proteins); 0 (RNA-Binding Proteins); 0 (Tumor Necrosis Factor-alpha); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.7.11.1 (RIPK3 protein, human); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 3.4.22.- (CASP8 protein, human); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180114
[St] Status:MEDLINE


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[PMID]:29276946
[Au] Autor:Sithara T; Dhanya BP; Arun KB; Sini S; Dan M; Kokkuvayil Vasu R; Nisha P
[Ad] Endereço:Agro Processing and Technology Division, National Institute for Interdisciplinary Science and Technology (CSIR-NIIST) , Thiruvananthapuram, Kerala 695019, India.
[Ti] Título:Zerumbone, a Cyclic Sesquiterpene from Zingiber zerumbet Induces Apoptosis, Cell Cycle Arrest, and Antimigratory Effects in SW480 Colorectal Cancer Cells.
[So] Source:J Agric Food Chem;66(3):602-612, 2018 Jan 24.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Zerumbone isolated from the rhizomes of Zingiber zerumbet was investigated for the mechanisms by which it exhibits antiproliferative activity in colorectal cancer cells (SW480). The results indicated that the zerumbone suppressed cell growth and enhanced cell apoptosis. Exposure to zerumbone induced generation of reactive oxygen species, reduced the cellular antioxidant status, decreased mitochondrial membrane potential, and activated caspase 3, caspase 8, and caspase 9 (p < 0.001). It was also found that there was a decrease in the expression of Bcl 2 and elevation of Bax (p < 0.001) on exposure to zerumbone. Furthermore, treatment with 50, 75, and 100 µM zerumbone resulted in cell cycle arrest at the G2/M phase with a value of 17.2 ± 0.1, 19.63 ± 0.25, and 26.66 ± 0.25, respectively, and also distorted the microfilament network and effectively inhibited cellular migration.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Movimento Celular/efeitos dos fármacos
Neoplasias Colorretais/fisiopatologia
Extratos Vegetais/farmacologia
Sesquiterpenos/farmacologia
Zingiberaceae/química
[Mh] Termos MeSH secundário: Caspase 3/genética
Caspase 3/metabolismo
Caspase 8/genética
Caspase 8/metabolismo
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/genética
Neoplasias Colorretais/metabolismo
Seres Humanos
Extratos Vegetais/isolamento & purificação
Proteínas Proto-Oncogênicas c-bcl-2/genética
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Sesquiterpenos/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Extracts); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Sesquiterpenes); 471-05-6 (zerumbone); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171226
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04472


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[PMID]:29191655
[Au] Autor:Li M; Yao J; Zhang X; Chen X; Chen J; Guan Y; Yang X
[Ad] Endereço:The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, PR China.
[Ti] Título:Q482H mutation of procaspase-8 in acute myeloid leukemia abolishes caspase-8-mediated apoptosis by impairing procaspase-8 dimerization.
[So] Source:Biochem Biophys Res Commun;495(1):1376-1382, 2018 01 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Certain procaspase-8 mutations are reported to be associated with the progression and prognosis of multiple tumors. However, it remains unclear whether the poor chemotherapy response and frequent relapse after complete remission of patients with acute myeloid leukemia (AML) is also related to procaspase-8 abnormalities. METHODS: Polymerase chain reaction (PCR) amplification and Sanger sequencing of the procaspase-8 gene (CASP8) were performed. Apoptotic rates were analyzed with Annexin V-FITC staining in cells expressing wild-type (WT) procaspase-8, the Q482H or C360S mutant, or control vector after treatment with or without tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Western blot analysis was performed to detect activation of procaspase-8 and downstream apoptotic signaling pathway components in those cells. The Co-immunoprecipitation (Co-IP) assays were performed to detect interaction between WT and mutant procaspase-8 proteins. RESULTS: AML patients carrying the Q482H mutation were likely to develop chemotherapy resistance. Similar to C360S, The Q482H mutation abolished caspase-8-mediated apoptotic signaling and inhibited TRAIL-induced apoptosis. The Q482H mutation impaired procaspase-8 dimerization, thus preventing the self-activation of procaspase-8. CONCLUSION: The procaspase-8 Q482H mutation in AML patients abolishes caspase-8-mediated apoptosis by impairing procaspase-8 dimerization.
[Mh] Termos MeSH primário: Apoptose/genética
Caspase 8/genética
Resistência a Medicamentos Antineoplásicos/genética
Leucemia Mieloide Aguda/genética
Leucemia Mieloide Aguda/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Dimerização
Feminino
Regulação Enzimológica da Expressão Gênica/genética
Regulação Neoplásica da Expressão Gênica/genética
Marcadores Genéticos/genética
Predisposição Genética para Doença/genética
Seres Humanos
Leucemia Mieloide Aguda/tratamento farmacológico
Masculino
Meia-Idade
Mutação/genética
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Genetic Markers); EC 3.4.22.- (CASP8 protein, human); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE


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[PMID]:29187437
[Au] Autor:Yanarojana M; Nararatwanchai T; Thairat S; Tancharoen S
[Ad] Endereço:School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, Bangkok, Thailand.
[Ti] Título:Antiproliferative Activity and Induction of Apoptosis in Human Melanoma Cells by Thunb Extract.
[So] Source:Anticancer Res;37(12):6619-6628, 2017 12.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: To analyze the apoptotic effect of Houttuynia cordata Thunb (HCT) extract on human melanoma A375 cells and its underlying mechanisms. MATERIALS AND METHODS: The effects of HCT on cell death were determined using the MTT assay. Hoechst 33342 staining was conducted to confirm the detection of cell apoptosis. Caspase-3 and caspase-8 mRNA and cleaved protein levels were investigated by RT-PCR and western blotting, respectively. The release of high mobility group box 1 (HMGB1) and phosphorylation of mitogen-activated protein kinase (MAPK) were determined by ELISA. RESULTS: Caspase-3 and caspase-8 specific inhibitors suppressed HCT-induced cell death. HCT increased caspase-3 and caspase-8 mRNA, protein levels, and caspase activities in a concentration- and time-dependent manner. HCT induced MAPK phosphorylation in a time-dependent fashion. Pretreatment of cells with a selective inhibitor of p38 MAPK reduced apoptosis and reversed the levels of HMGB1 release in response to HCT treatment. CONCLUSION: HCT induces A375 programmed cell death by activating the caspase-dependent pathway and by p38 phosphorylation associated with HMGB1 reduction.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Houttuynia/química
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: Western Blotting
Caspase 3/genética
Caspase 3/metabolismo
Caspase 8/genética
Caspase 8/metabolismo
Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Melanoma/genética
Melanoma/metabolismo
Melanoma/patologia
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Fosforilação/efeitos dos fármacos
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Extracts); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


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[PMID]:27777194
[Au] Autor:Huang H; Tian ZT; Yao YM; Li TS
[Ad] Endereço:1Emergency Department, Chinese PLA General Hospital, Beijing 100853, China; 2Department of Critical Care Medicine, General Hospital of Jinan Command, Jinan 250031, China. E-mail: huanghe_hh@126.com.
[Ti] Título:[Tumor necrosis factor-α-induced protein 8 like-2 promotes apoptosis of CD4 T lymphocytes in mice with severe burn injury].
[So] Source:Nan Fang Yi Ke Da Xue Xue Bao;36(10):1334-1339, 2016 Oct 20.
[Is] ISSN:1673-4254
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To investigate the effect of tumor necrosis factor-α-induced protein 8 like-2 (TIPE2) on apoptosis of CD4 T lymphocytes in a murine model of severe burn injury. METHODS: A total of 140 male mice were randomly allocated into 6 groups. Small RNA interference technique was used to construct a siTIPE2-overexpressing lentivirus, and severe burn injury models were established in the mice. CD4 T cells were purified from spleen of the mice, and the expressions of TIPE2, Smad2/Smad3, P-Smad2/P-Smad3 and Bcl-2/Bimprotein in CD4 Tregs were detected. The changes in mitochondrial membrane potential and cytochrome C in CD4 T cells were detected, and the activities of caspase-3, caspase-8, and caspase-9 were analyzed. RESULTS: Down-regulation of TIPE2 promoted the apoptosis of CD4 T lymphocytes in siTIPE2-burn group, in which the protein expressions of P-smad2/P-Smad3 decreased, Bcl-2 expression increased and Bim expression decreased significantly as compared with the other groups (P<0.01 or 0.05). The mitochondrial membrane potential and cytochrome C expression in CD4 T cells were down-regulated in siTIPE2-burn group (P<0.05) with a lowered caspase-3 activity compared with TIPE2-burn group (P<0.01) and decreased caspase-8 and caspase-9 compared with the other groups (P<0.05). The apoptosis rate was the highest in TIPE2-burn group, whose Smad2/Smad3 was higher than that in the sham group (P<0.05) and the expression of P-smad2/P-Smad3 significantly increased compared with the other groups (P<0.05). In TIPE2-burn group, the mitochondrial membrane potential in CD4 T cells was decreased (P<0.01), the expression of cytochrome C increased markedly (P<0.01), and the activities of caspase-3, caspase-8, and caspase-9 were all obviously higher than those in the other groups (P<0.05). CONCLUSION: As an important immunoregulatory molecule, TIPE2 can promote the apoptosis of CD4 T lymphocyte in mice with sever burn injury.
[Mh] Termos MeSH primário: Apoptose
Queimaduras/imunologia
Linfócitos T CD4-Positivos/citologia
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
[Mh] Termos MeSH secundário: Animais
Caspase 3/metabolismo
Caspase 8/metabolismo
Caspase 9/metabolismo
Regulação para Baixo
Masculino
Camundongos
Proteína Smad2/metabolismo
Proteína Smad3/metabolismo
Baço
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Smad2 Protein); 0 (Smad2 protein, mouse); 0 (Smad3 Protein); 0 (Smad3 protein, mouse); 0 (TIPE2 protein, mouse); EC 3.4.22.- (Casp3 protein, mouse); EC 3.4.22.- (Casp8 protein, mouse); EC 3.4.22.- (Casp9 protein, mouse); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8); EC 3.4.22.- (Caspase 9)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  9 / 5262 MEDLINE  
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[PMID]:28985224
[Au] Autor:Rehker J; Rodhe J; Nesbitt RR; Boyle EA; Martin BK; Lord J; Karaca I; Naj A; Jessen F; Helisalmi S; Soininen H; Hiltunen M; Ramirez A; Scherer M; Farrer LA; Haines JL; Pericak-Vance MA; Raskind WH; Cruchaga C; Schellenberg GD; Joseph B; Brkanac Z
[Ad] Endereço:Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States of America.
[Ti] Título:Caspase-8, association with Alzheimer's Disease and functional analysis of rare variants.
[So] Source:PLoS One;12(10):e0185777, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The accumulation of amyloid beta (Aß) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p.K148R and p.I298V, the association remained significant in a combined sample of 10,820 cases and 8,881 controls. For both variants we performed bioinformatics structural, expression and enzymatic activity studies and obtained evidence for loss of function effects. In addition to their role in amyloid processing, caspase-8 and its downstream effector caspase-3 are involved in synaptic plasticity, learning, memory and control of microglia pro-inflammatory activation and associated neurotoxicity, indicating additional mechanisms that might contribute to AD. As caspase inhibition has been proposed as a mechanism for AD treatment, our finding that AD-associated CASP8 variants reduce caspase function calls for caution and is an impetus for further studies on the role of caspases in AD and other neurodegenerative diseases.
[Mh] Termos MeSH primário: Alelos
Doença de Alzheimer/genética
Caspase 8/genética
Variação Genética
[Mh] Termos MeSH secundário: Doença de Alzheimer/metabolismo
Estudos de Casos e Controles
Caspase 8/metabolismo
Linhagem Celular Tumoral
Frequência do Gene
Estudos de Associação Genética
Predisposição Genética para Doença
Seres Humanos
Neurônios/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185777


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[PMID]:28898696
[Au] Autor:Boege Y; Malehmir M; Healy ME; Bettermann K; Lorentzen A; Vucur M; Ahuja AK; Böhm F; Mertens JC; Shimizu Y; Frick L; Remouchamps C; Mutreja K; Kähne T; Sundaravinayagam D; Wolf MJ; Rehrauer H; Koppe C; Speicher T; Padrissa-Altés S; Maire R; Schattenberg JM; Jeong JS; Liu L; Zwirner S; Boger R; Hüser N; Davis RJ; Müllhaupt B; Moch H; Schulze-Bergkamen H; Clavien PA; Werner S; Borsig L; Luther SA; Jost PJ; Weinlich R; Unger K; Behrens A; Hillert L; Dillon C; Di Virgilio M; Wallach D; Dejardin E; Zender L; Naumann M; Walczak H; Green DR; Lopes M; Lavrik I
[Ad] Endereço:Department of Pathology and Molecular Pathology, University and University Hospital Zurich, 8091 Zurich, Switzerland.
[Ti] Título:A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development.
[So] Source:Cancer Cell;32(3):342-359.e10, 2017 Sep 11.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
[Mh] Termos MeSH primário: Carcinogênese/metabolismo
Carcinogênese/patologia
Caspase 8/metabolismo
Dano ao DNA
Neoplasias Hepáticas/enzimologia
Neoplasias Hepáticas/patologia
[Mh] Termos MeSH secundário: Animais
Apoptose
Carcinoma Hepatocelular/patologia
Proliferação Celular
Senescência Celular
Doença Crônica
Cruzamentos Genéticos
Reparo do DNA
Proteína de Domínio de Morte Associada a Fas/metabolismo
Feminino
Instabilidade Genômica
Hepatectomia
Hepatócitos/patologia
Histonas/metabolismo
Seres Humanos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo
Fígado/metabolismo
Fígado/patologia
Regeneração Hepática
Masculino
Camundongos
Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo
Fosforilação
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fadd protein, mouse); 0 (Fas-Associated Death Domain Protein); 0 (Histones); 0 (Mcl1 protein, mouse); 0 (Myeloid Cell Leukemia Sequence 1 Protein); 0 (Receptors, Tumor Necrosis Factor, Type I); 0 (gamma-H2AX protein, mouse); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 2.7.11.1 (Ripk1 protein, mouse); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE



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