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[PMID]:28815695
[Au] Autor:Sahoo R; Ghosh P; Chorev M; Halperin JA
[Ad] Endereço:Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
[Ti] Título:A distinctive histidine residue is essential for in vivo glycation-inactivation of human CD59 transgenically expressed in mice erythrocytes: Implications for human diabetes complications.
[So] Source:Am J Hematol;92(11):1198-1203, 2017 Nov.
[Is] ISSN:1096-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced É›-amino glycation of Lys . Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of É›-amino lysyl residues occurs predominantly at "glycation motives" that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5Å from the É›-amino group. hCD59 contains a distinctive Lys /His putative glycation motif within its active site. In a model of transgenic diabetic mice expressing in erythrocytes either the wild type or a H44Q mutant form of hCD59, we demonstrate in vivo that the His is required for Lys glycation and consequent functional inactivation of hCD59, as evidenced using a mouse erythrocytes hemolytic assay. Since (1) the His residue is not present in CD59 from other animal species and (2) humans are particularly prone to develop complications of diabetes, our results indicate that the Lys /His glycation motif in human CD59 may confer humans a higher risk of developing vascular disease in response to hyperglycemia.
[Mh] Termos MeSH primário: Antígenos CD59/genética
Antígenos CD59/metabolismo
Eritrócitos/metabolismo
Regulação da Expressão Gênica
Histidina/metabolismo
[Mh] Termos MeSH secundário: Animais
Glicemia
Complicações do Diabetes/genética
Complicações do Diabetes/metabolismo
Diabetes Mellitus Experimental
Membrana Eritrocítica/metabolismo
Glicosilação
Hemólise
Humanos
Lisina/metabolismo
Camundongos
Camundongos Transgênicos
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Blood Glucose); 101754-01-2 (CD59 protein, human); 4QD397987E (Histidine); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE
[do] DOI:10.1002/ajh.24886


  2 / 1459 MEDLINE  
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[PMID]:28622911
[Au] Autor:Tabib A; Karbian N; Mevorach D
[Ad] Endereço:Rheumatology Research Center and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
[Ti] Título:Demyelination, strokes, and eculizumab: Lessons from the congenital CD59 gene mutations.
[So] Source:Mol Immunol;89:69-72, 2017 Sep.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Neurological symptoms of patients with p.Cys89Tyr mutation in the CD59 gene include recurrent peripheral neuropathy resembling Guillain-Barré syndrome, characterized by sensory-motor demyelinating neuropathy with secondary axonal damage and moderate enhancement of the nerve roots on spine MRI, together with recurrent strokes and retinal involvement. Three additional mutations in CD59, leading to loss of function, have been described, and overall, 12/12 (100%) of patients with any mutation presented with neurological symptoms; 11/12 (92%) patients presented with recurrent peripheral neuropathy, 6/12 (50%) with recurrent strokes, and 1/12 (8%) with retinal involvement. We review the possible thrombophilic profile associated with the mutations. In these patients, excessive intravascular hemolysis saturates scavenger mechanisms resulting in free hemoglobin in plasma that irreversibly reacts with nitric oxide to form nitrate and methemoglobin, leading to arterial thrombosis. CD59 loss of function is also one of the major thrombophilic mechanisms in patients with paroxysmal nocturnal hemoglobinuria. We then describe the relationship with demyelination. The lack of CD59 allows uncontrolled complement amplification following low-level spontaneous-, viral-, or post viral-induced complement activation, resulting in severe demyelination in the peripheral nervous system. It is interesting, and certainly encouraging, that after 3 years, following 4 patients with Cys89Tyr mutations who are treated with eculizumab, no strokes occurred and non-permanent neurological insults underwent resolution without any new neurological exacerbations.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/uso terapêutico
Antígenos CD59/genética
Doenças Desmielinizantes/quimioterapia
Mutação
Acidente Vascular Cerebral/quimioterapia
[Mh] Termos MeSH secundário: Ativação do Complemento/efeitos de drogas
Inativadores do Complemento/uso terapêutico
Doenças Desmielinizantes/genética
Humanos
Acidente Vascular Cerebral/genética
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD59); 0 (Complement Inactivating Agents); 101754-01-2 (CD59 protein, human); A3ULP0F556 (eculizumab)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE


  3 / 1459 MEDLINE  
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[PMID]:28922377
[Au] Autor:Lepik K; Annilo T; Kukuskina V; Kisand K; Kutalik Z; Peterson P; Peterson H; eQTLGen Consortium
[Ad] Endereço:Institute of Computer Science, University of Tartu, Tartu, Estonia.
[Ti] Título:C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis.
[So] Source:PLoS Comput Biol;13(9):e1005766, 2017 09.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits.
[Mh] Termos MeSH primário: Antígenos CD59/metabolismo
Proteína C-Reativa/metabolismo
[Mh] Termos MeSH secundário: Adulto
Antígenos CD59/sangue
Estudos de Coortes
Estônia
Humanos
Inflamação/metabolismo
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 101754-01-2 (CD59 protein, human); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170918
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005766


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[PMID]:28330937
[Au] Autor:Kinoshita M; Suzuki KG; Matsumori N; Takada M; Ano H; Morigaki K; Abe M; Makino A; Kobayashi T; Hirosawa KM; Fujiwara TK; Kusumi A; Murata M
[Ad] Endereço:Lipid Active Structure Project, Exploratory Research for Advanced Technology Organization, Japan Science and Technology Agency, Osaka University, Osaka 560-0043, Japan.
[Ti] Título:Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs.
[So] Source:J Cell Biol;216(4):1183-1204, 2017 Apr 03.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sphingomyelin (SM) has been proposed to form cholesterol-dependent raft domains and sphingolipid domains in the plasma membrane (PM). How SM contributes to the formation and function of these domains remains unknown, primarily because of the scarcity of suitable fluorescent SM analogs. We developed new fluorescent SM analogs by conjugating a hydrophilic fluorophore to the SM choline headgroup without eliminating its positive charge, via a hydrophilic nonaethylene glycol linker. The new analogs behaved similarly to the native SM in terms of their partitioning behaviors in artificial liquid order-disorder phase-separated membranes and detergent-resistant PM preparations. Single fluorescent molecule tracking in the live-cell PM revealed that they indirectly interact with each other in cholesterol- and sphingosine backbone-dependent manners, and that, for ∼10-50 ms, they undergo transient colocalization-codiffusion with a glycosylphosphatidylinositol (GPI)-anchored protein, CD59 (in monomers, transient-dimer rafts, and clusters), in CD59-oligomer size-, cholesterol-, and GPI anchoring-dependent manners. These results suggest that SM continually and rapidly exchanges between CD59-associated raft domains and the bulk PM.
[Mh] Termos MeSH primário: Corantes Fluorescentes/metabolismo
Esfingomielinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/metabolismo
Células CHO
Linhagem Celular
Membrana Celular/metabolismo
Colesterol/metabolismo
Cricetulus
Detergentes/metabolismo
Glicosilfosfatidilinositóis/metabolismo
Interações Hidrofóbicas e Hidrofílicas
Microdomínios da Membrana/metabolismo
Esfingolipídeos/metabolismo
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Detergents); 0 (Fluorescent Dyes); 0 (Glycosylphosphatidylinositols); 0 (Sphingolipids); 0 (Sphingomyelins); 101754-01-2 (CD59 protein, human); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201607086


  5 / 1459 MEDLINE  
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[PMID]:27979168
[Au] Autor:Ji X; Li X; Ma Y; Li D
[Ad] Endereço:School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150090, China.
[Ti] Título:Differences in proteomic profiles of milk fat globule membrane in yak and cow milk.
[So] Source:Food Chem;221:1822-1827, 2017 Apr 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Milk fat globule membrane (MFGM) is an important milk component which is rich in bioactive proteins. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approach was used to investigate the differences in the MFGM proteins between yak and cow milk. Over 450 proteins were identified between the yak and cow MFGM. The MFGM proteins with significant differences were compared based on the relative abundance. Proteins such as Glycosylation-dependent cell adhesion molecule 1 (GlyCAM1), CD59 molecule and lactadherin, were identified having a much higher abundance (4.6-10.1 fold) in yak MFGM than cow MFGM. These proteins are thought to have biological functions such as the antimicrobial and antitumor effects. This may be due to the need that yak produces high nutritive milk including high levels of bioactive compounds in order to resist the extreme high altitude environment.
[Mh] Termos MeSH primário: Glicolipídeos/química
Glicoproteínas/química
Leite/química
Proteômica
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/química
Bovinos/classificação
Feminino
Proteínas do Leite/química
Mucinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Glycolipids); 0 (Glycoproteins); 0 (Milk Proteins); 0 (Mucins); 0 (milk fat globule); 145895-89-2 (sulfated glycoprotein p50)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE


  6 / 1459 MEDLINE  
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[PMID]:28500075
[Au] Autor:Bongoni AK; Lu B; Salvaris EJ; Roberts V; Fang D; McRae JL; Fisicaro N; Dwyer KM; Cowan PJ
[Ad] Endereço:Immunology Research Centre, St. Vincent's Hospital Melbourne, Fitzroy, Victoria 3065, Australia.
[Ti] Título:Overexpression of Human CD55 and CD59 or Treatment with Human CD55 Protects against Renal Ischemia-Reperfusion Injury in Mice.
[So] Source:J Immunol;198(12):4837-4845, 2017 Jun 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Deficiency in the membrane-bound complement regulators CD55 and CD59 exacerbates renal ischemia-reperfusion injury (IRI) in mouse models, but the effect of increasing CD55 and CD59 activity has not been examined. In this study, we investigated the impact of overexpression of human (h) CD55 ± hCD59 or treatment with soluble rhCD55 in a mouse model of renal IRI. Unilaterally nephrectomised mice were subjected to 18 (mild IRI) or 22 min (moderate IRI) warm renal ischemia, and analyzed 24 h after reperfusion for renal function (serum creatinine and urea), complement deposition (C3b/c and C9), and infiltration of neutrophils and macrophages. Transgenic mice expressing hCD55 alone were protected against mild renal IRI, with reduced creatinine and urea levels compared with wild type littermates. However, the renal function of the hCD55 mice was not preserved in the moderate IRI model, despite a reduction in C3b/c and C9 deposition and innate cell infiltration. Mice expressing both hCD55 and hCD59, on the other hand, were protected in the moderate IRI model, with significant reductions in all parameters measured. Wild type mice treated with rhCD55 immediately after reperfusion were also protected in the moderate IRI model. Thus, manipulation of CD55 activity to increase inhibition of the C3 and C5 convertases is protective against renal IRI, and the additional expression of hCD59, which regulates the terminal complement pathway, provides further protection. Therefore, anti-complement therapy using complement regulatory proteins may provide a potential clinical option for preventing tissue and organ damage in renal IRI.
[Mh] Termos MeSH primário: Antígenos CD55/genética
Antígenos CD55/uso terapêutico
Antígenos CD59/genética
Nefropatias/terapia
Traumatismo por Reperfusão/terapia
[Mh] Termos MeSH secundário: Animais
Antígenos CD55/imunologia
Ativação do Complemento
Creatinina/sangue
Humanos
Nefropatias/imunologia
Nefropatias/fisiopatologia
Macrófagos/imunologia
Camundongos
Camundongos Transgênicos
Neutrófilos/imunologia
Traumatismo por Reperfusão/imunologia
Traumatismo por Reperfusão/fisiopatologia
Ureia/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD55); 0 (Antigens, CD59); 101754-01-2 (CD59 protein, human); 8W8T17847W (Urea); AYI8EX34EU (Creatinine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601943


  7 / 1459 MEDLINE  
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[PMID]:28516949
[Au] Autor:Hill A; DeZern AE; Kinoshita T; Brodsky RA
[Ad] Endereço:Department of Haematology, St. James' University Hospital, Leeds, UK.
[Ti] Título:Paroxysmal nocturnal haemoglobinuria.
[So] Source:Nat Rev Dis Primers;3:17028, 2017 May 18.
[Is] ISSN:2056-676X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell (HSC) disease that presents with haemolytic anaemia, thrombosis and smooth muscle dystonias, as well as bone marrow failure in some cases. PNH is caused by somatic mutations in PIGA (which encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors. Clinical manifestations of PNH occur when a HSC clone carrying somatic PIGA mutations acquires a growth advantage and differentiates, generating mature blood cells that are deficient of GPI-anchored proteins. The loss of CD55 and CD59 renders PNH erythrocytes susceptible to intravascular haemolysis, which can lead to thrombosis and to much of the morbidity and mortality of PNH. The accumulation of anaphylatoxins (such as C5a) from complement activation might also have a role. The natural history of PNH is highly variable, ranging from quiescent to life-threatening. Therapeutic strategies include terminal complement blockade and bone marrow transplantation. Eculizumab, a monoclonal antibody complement inhibitor, is highly effective and the only licensed therapy for PNH.
[Mh] Termos MeSH primário: Hemoglobinúria Paroxística/patologia
Hemoglobinúria Paroxística/terapia
Proteínas de Membrana/genética
[Mh] Termos MeSH secundário: Anticorpos Monoclonais Humanizados/uso terapêutico
Antígenos CD55/metabolismo
Antígenos CD59/metabolismo
Transplante de Medula Óssea
Proteínas Inativadoras do Complemento/metabolismo
Hemoglobinúria Paroxística/genética
Hemoglobinúria Paroxística/metabolismo
Humanos
Mutação
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD55); 0 (Antigens, CD59); 0 (Complement Inactivator Proteins); 0 (Membrane Proteins); 0 (phosphatidylinositol glycan-class A protein); 101754-01-2 (CD59 protein, human); A3ULP0F556 (eculizumab)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1038/nrdp.2017.28


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[PMID]:28714084
[Au] Autor:Ji Z; LeBaron MJ
[Ad] Endereço:Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, 48674.
[Ti] Título:Applying the erythrocyte Pig-a assay concept to rat epididymal sperm for germ cell mutagenicity evaluation.
[So] Source:Environ Mol Mutagen;58(7):485-493, 2017 Aug.
[Is] ISSN:1098-2280
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Pig-a assay, a recently developed in vivo somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)-anchored cell surface markers. We hypothesized that the erythrocyte Pig-a assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI-anchored CD59 as the Pig-a mutation marker and examined the frequency of CD59-negative sperm using flow cytometry. A reconstruction experiment that spiked un-labeled sperm (mutant-mimic) into labeled sperm at specific ratios yielded good agreement between the detected and expected frequencies of mutant-mimic sperm, demonstrating the analytical ability for CD59-negative sperm detection. Furthermore, this methodology was assessed in F344/DuCrl rats administered N-ethyl-N-nitrosourea (ENU), a prototypical mutagen, or clofibrate, a lipid-lowering drug. Rats treated with 1, 10, or 20 mg/kg body weight/day (mkd) ENU via daily oral garage for five consecutive days showed a dose-dependent increase in the frequency of CD59-negative sperm on study day 63 (i.e., 58 days after the last ENU dose). This ENU dosing regimen also increased the frequency of CD59-negative erythrocytes. In rats treated with 300 mkd clofibrate via daily oral garage for consecutive 28 days, no treatment-related changes were detected in the frequency of CD59-negative sperm on study day 85 (i.e., 57 days after the last dose) or in the frequency of CD59-negative erythrocytes on study day 29. In conclusion, these data suggest that the epidiymal sperm Pig-a assay in rats is a promising method for evaluating germ cell mutagenicity. Environ. Mol. Mutagen. 58:485-493, 2017. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Epididimo
Proteínas de Membrana/genética
Testes de Mutagenicidade/métodos
Mutagênicos/toxicidade
Espermatozoides/efeitos de drogas
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/genética
Clofibrato/toxicidade
Eritrócitos/efeitos de drogas
Eritrócitos/metabolismo
Eritrócitos/patologia
Etilnitrosoureia/toxicidade
Citometria de Fluxo
Glicosilfosfatidilinositóis/biossíntese
Masculino
Ratos Endogâmicos F344
Espermatozoides/metabolismo
Espermatozoides/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Glycosylphosphatidylinositols); 0 (Membrane Proteins); 0 (Mutagens); 0 (phosphatidylinositol glycan-class A protein); HPN91K7FU3 (Clofibrate); P8M1T4190R (Ethylnitrosourea)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170717
[St] Status:MEDLINE
[do] DOI:10.1002/em.22109


  9 / 1459 MEDLINE  
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[PMID]:28533125
[Au] Autor:Hoffman WH; Artlett CM; Boodhoo D; Gilliland MGF; Ortiz L; Mulder D; Tjan DHT; Martin A; Tatomir A; Rus H
[Ad] Endereço:Department of Pediatrics, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States. Electronic address: whoffman@augusta.edu.
[Ti] Título:Markers of immune-mediated inflammation in the brains of young adults and adolescents with type 1 diabetes and fatal diabetic ketoacidosis. Is there a difference?
[So] Source:Exp Mol Pathol;102(3):505-514, 2017 Jun.
[Is] ISSN:1096-0945
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0.03). CD59, a MAC assembly inhibitory protein was absent, possibly suppressed by the hyperglycemia in the teenagers but was expressed in the young adults despite comparable average levels of hyperglycemia. The receptor for advanced glycation end products (RAGE) had an average expression in the young adults significantly greater than in the teenagers (p=0.02). The autophagy marker Light Chain 3 (LC3) A/B was the predominant form of programmed cell death (PCD) in the teenage brains. The young adults had high expressions of both LC3A/B and TUNEL, an apoptotic cell marker for DNA fragmentation. BE was present in the newly diagnosed young adult with hyperglycemic hyperosmolar DKA and also in the two teenagers. Our data indicate that significant differences in neuroinflammatory components, initiated by the dysregulation of DKA and interrelated metabolic and immunologic milieu, are likely present in the brains of fatal DKA of teenagers when compared with young adults.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Diabetes Mellitus Tipo 1/genética
Cetoacidose Diabética/genética
Inflamação Neurogênica/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antígenos CD59/genética
Antígenos CD59/metabolismo
Autofagia
Encéfalo/fisiopatologia
Edema Encefálico/diagnóstico
Edema Encefálico/etiologia
Edema Encefálico/genética
Fragmentação do DNA
Diabetes Mellitus Tipo 1/complicações
Cetoacidose Diabética/complicações
Regulação da Expressão Gênica
Humanos
Imuno-Histoquímica
Marcação In Situ das Extremidades Cortadas
Mediadores da Inflamação/metabolismo
Proteínas Associadas aos Microtúbulos/genética
Proteínas Associadas aos Microtúbulos/metabolismo
Inflamação Neurogênica/etiologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (Biomarkers); 0 (Inflammation Mediators); 0 (Microtubule-Associated Proteins); 0 (light chain 3, human); 101754-01-2 (CD59 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE


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[PMID]:28345259
[Au] Autor:Blom AM
[Ad] Endereço:Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, Sweden.
[Ti] Título:The role of complement inhibitors beyond controlling inflammation.
[So] Source:J Intern Med;282(2):116-128, 2017 Aug.
[Is] ISSN:1365-2796
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The complement system is an arm of innate immunity that aids in the removal of pathogens and dying cells. Due to its harmful, pro-inflammatory potential, complement is controlled by several soluble and membrane-bound inhibitors. This family of complement regulators has been recently extended by the discovery of several new members, and it is becoming apparent that these proteins harbour additional functions. In this review, the current state of knowledge of the physiological functions of four complement regulators will be described: cartilage oligomeric matrix protein (COMP), CUB and sushi multiple domains 1 (CSMD1), sushi domain-containing protein 4 (SUSD4) and CD59. Complement activation is involved in both the development of and defence against cancer. COMP expression is pro-oncogenic, whereas CSMD1 and SUSD4 act as tumour suppressors. These effects may be related in part to the complex influence of complement on cancer but also depend on unrelated functions such as the protection of cells from endoplasmic reticulum stress conveyed by intracellular COMP. CD59 is the main inhibitor of the membrane attack complex, and its deficiency leads to complement attack on erythrocytes and severe haemolytic anaemia, which is now amenable to treatment with an inhibitor of C5 cleavage. Unexpectedly, the intracellular pool of CD59 is crucial for insulin secretion from pancreatic ß-cells. This finding is one of several relating to the intracellular functions of complement proteins, which until recently were only considered to be present in the extracellular space. Understanding the alternative functions of complement inhibitors may unravel unexpected links between complement and other physiological systems, but is also important for better design of therapeutic complement inhibition.
[Mh] Termos MeSH primário: Proteínas do Sistema Complemento/fisiologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD59/fisiologia
Proteína de Matriz Oligomérica de Cartilagem/fisiologia
Ativação do Complemento/fisiologia
Proteínas Inativadoras do Complemento/fisiologia
Humanos
Infecção/fisiopatologia
Inflamação/fisiopatologia
Artropatias/fisiopatologia
Proteínas de Membrana/fisiologia
Neoplasias/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, CD59); 0 (COMP protein, human); 0 (CSMD1 protein, human); 0 (Cartilage Oligomeric Matrix Protein); 0 (Complement Inactivator Proteins); 0 (Membrane Proteins); 0 (SUSD4 protein, human); 9007-36-7 (Complement System Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170327
[St] Status:MEDLINE
[do] DOI:10.1111/joim.12606



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