Base de dados : MEDLINE
Pesquisa : D08.811.277.040.013.500.032 [Categoria DeCS]
Referências encontradas : 734 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 74 ir para página                         

  1 / 734 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29281627
[Au] Autor:Schramm FD; Heinrich K; Thüring M; Bernhardt J; Jonas K
[Ad] Endereço:Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
[Ti] Título:An essential regulatory function of the DnaK chaperone dictates the decision between proliferation and maintenance in Caulobacter crescentus.
[So] Source:PLoS Genet;13(12):e1007148, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hsp70 chaperones are well known for their important functions in maintaining protein homeostasis during thermal stress conditions. In many bacteria the Hsp70 homolog DnaK is also required for growth in the absence of stress. The molecular reasons underlying Hsp70 essentiality remain in most cases unclear. Here, we demonstrate that DnaK is essential in the α-proteobacterium Caulobacter crescentus due to its regulatory function in gene expression. Using a suppressor screen we identified mutations that allow growth in the absence of DnaK. All mutations reduced the activity of the heat shock sigma factor σ32, demonstrating that the DnaK-dependent inactivation of σ32 is a growth requirement. While most mutations occurred in the rpoH gene encoding σ32, we also identified mutations affecting σ32 activity or stability in trans, providing important new insight into the regulatory mechanisms controlling σ32 activity. Most notably, we describe a mutation in the ATP dependent protease HslUV that induces rapid degradation of σ32, and a mutation leading to increased levels of the house keeping σ70 that outcompete σ32 for binding to the RNA polymerase. We demonstrate that σ32 inhibits growth and that its unrestrained activity leads to an extensive reprogramming of global gene expression, resulting in upregulation of repair and maintenance functions and downregulation of the growth-promoting functions of protein translation, DNA replication and certain metabolic processes. While this re-allocation from proliferative to maintenance functions could provide an advantage during heat stress, it leads to growth defects under favorable conditions. We conclude that Caulobacter has co-opted the DnaK chaperone system as an essential regulator of gene expression under conditions when its folding activity is dispensable.
[Mh] Termos MeSH primário: Caulobacter crescentus/fisiologia
Proteínas de Choque Térmico HSP70/fisiologia
[Mh] Termos MeSH secundário: Proteases Dependentes de ATP/genética
Sequência de Aminoácidos
Proteínas de Bactérias/genética
Caulobacter crescentus/genética
Caulobacter crescentus/metabolismo
RNA Polimerases Dirigidas por DNA/genética
Regulação Bacteriana da Expressão Gênica
Proteínas de Choque Térmico HSP40/genética
Proteínas de Choque Térmico HSP70/genética
Proteínas de Choque Térmico HSP70/metabolismo
Resposta ao Choque Térmico
Chaperonas Moleculares/genética
Fator sigma/genética
Fatores de Transcrição/genética
Transcrição Genética/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (HSP40 Heat-Shock Proteins); 0 (HSP70 Heat-Shock Proteins); 0 (Molecular Chaperones); 0 (Sigma Factor); 0 (Transcription Factors); EC 2.7.7.6 (DNA-Directed RNA Polymerases); EC 3.4.21.- (ATP-Dependent Proteases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007148


  2 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29180014
[Au] Autor:An JY; Sharif H; Kang GB; Park KJ; Lee JG; Lee S; Jin MS; Song JJ; Wang J; Eom SH
[Ad] Endereço:School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea; Steitz Center for Structural Biology, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
[Ti] Título:Structural insights into the oligomerization of FtsH periplasmic domain from Thermotoga maritima.
[So] Source:Biochem Biophys Res Commun;495(1):1201-1207, 2018 01 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. The transmembrane protein, FtsH, is the only known ATP-dependent protease responsible for this task. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. The structure and function of the ATPase and protease domains of FtsH have been previously characterized while the role of the FtsH periplasmic domain has not clearly identified. Here, we report the 1.5-1.95 Å resolution crystal structures of the Thermotoga maritima FtsH periplasmic domain (tmPD) and describe the dynamic features of tmPD oligomerization.
[Mh] Termos MeSH primário: Proteases Dependentes de ATP/química
Proteases Dependentes de ATP/ultraestrutura
Peptídeo Hidrolases/química
Peptídeo Hidrolases/ultraestrutura
Multimerização Proteica
Thermotoga maritima/enzimologia
[Mh] Termos MeSH secundário: Sítios de Ligação
Simulação por Computador
Ativação Enzimática
Modelos Químicos
Modelos Moleculares
Ligação Proteica
Conformação Proteica
Domínios Proteicos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.4.- (Peptide Hydrolases); EC 3.4.21.- (ATP-Dependent Proteases)
[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:171129
[St] Status:MEDLINE


  3 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28442264
[Au] Autor:Sepuri NBV; Angireddy R; Srinivasan S; Guha M; Spear J; Lu B; Anandatheerthavarada HK; Suzuki CK; Avadhani NG
[Ad] Endereço:Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6009, USA.
[Ti] Título:Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits under hypoxia and myocardial ischemia.
[So] Source:Biochim Biophys Acta;1858(7):519-528, 2017 07.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The mitochondrial ATP dependent matrix protease, Lon, is involved in the maintenance of mitochondrial DNA nucleoids and degradation of abnormal or misfolded proteins. The Lon protease regulates mitochondrial Tfam (mitochondrial transcription factor A) level and thus modulates mitochondrial DNA (mtDNA) content. We have previously shown that hypoxic stress induces the PKA-dependent phosphorylation of cytochrome c oxidase (CcO) subunits I, IVi1, and Vb and a time-dependent reduction of these subunits in RAW 264.7 murine macrophages subjected to hypoxia and rabbit hearts subjected to ischemia/reperfusion. Here, we show that Lon is involved in the preferential turnover of phosphorylated CcO subunits under hypoxic/ischemic stress. Induction of Lon protease occurs at 6 to 12 h of hypoxia and this increase coincides with lower CcO subunit contents. Over-expression of flag-tagged wild type and phosphorylation site mutant Vb and IVi1 subunits (S40A and T52A, respectively) caused marked degradation of wild type protein under hypoxia while the mutant proteins were relatively resistant. Furthermore, the recombinant purified Lon protease degraded the phosphorylated IVi1 and Vb subunits, while the phosphorylation-site mutant proteins were resistant to degradation. 3D structural modeling shows that the phosphorylation sites are exposed to the matrix compartment, accessible to matrix PKA and Lon protease. Hypoxic stress did not alter CcO subunit levels in Lon depleted cells, confirming its role in CcO turnover. Our results therefore suggest that Lon preferentially degrades the phosphorylated subunits of CcO and plays a role in the regulation of CcO activity in hypoxia and ischemia/reperfusion injury.
[Mh] Termos MeSH primário: Proteases Dependentes de ATP/metabolismo
Hipóxia Celular/fisiologia
Complexo IV da Cadeia de Transporte de Elétrons/metabolismo
Mitocôndrias Cardíacas/enzimologia
Proteínas Mitocondriais/metabolismo
Isquemia Miocárdica/enzimologia
[Mh] Termos MeSH secundário: Proteases Dependentes de ATP/química
Proteases Dependentes de ATP/genética
Animais
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
Seres Humanos
Masculino
Camundongos
Proteínas Mitocondriais/química
Proteínas Mitocondriais/genética
Modelos Moleculares
Fosforilação
Conformação Proteica
Processamento de Proteína Pós-Traducional
Subunidades Proteicas
Células RAW 264.7
Interferência de RNA
RNA Interferente Pequeno/genética
Coelhos
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (Protein Subunits); 0 (RNA, Small Interfering); 0 (Recombinant Proteins); EC 1.9.3.1 (Electron Transport Complex IV); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.21.- (LONP1 protein, human); EC 3.4.21.53 (LONP1 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


  4 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28315685
[Au] Autor:Yano M
[Ad] Endereço:Department of Medical Technology, Faculty of Health Sciences, Kumamoto Health Science University, Kumamoto 861-5598, Japan. Electronic address: yano@kumamoto-hsu.ac.jp.
[Ti] Título:ABCB10 depletion reduces unfolded protein response in mitochondria.
[So] Source:Biochem Biophys Res Commun;486(2):465-469, 2017 Apr 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondria have many functions, including ATP generation. The electron transport chain (ETC) and the coupled ATP synthase generate ATP by consuming oxygen. Reactive oxygen species (ROS) are also produced by ETC, and ROS damage deoxyribonucleic acids, membrane lipids and proteins. Recent analysis indicate that mitochondrial unfolded protein response (UPR ), which enhances expression of mitochondrial chaperones and proteases to remove damaged proteins, is activated when damaged proteins accumulate in the mitochondria. In Caenorhabditis elegans, HAF-1, a putative ortholog of human ABCB10, plays an essential role in signal transduction from mitochondria to nuclei to enhance UPR . Therefore, it is possible that ABCB10 has a role similar to that of HAF-1. However, it has not been reported whether ABCB10 is a factor in the signal transduction pathway to enhance UPR . In this study, ABCB10 was depleted in HepG2 cells using small interfering RNA (siRNA), and the effect was examined. ABCB10 depletion upregulated ROS and the expression of ROS-detoxifying enzymes (SOD2, GSTA1, and GSTA2), and SESN3, a protein induced by ROS to protect the cell from oxidative stress. In addition, ABCB10 depletion significantly decreased expression of UPR -related mitochondrial chaperones (HSPD1 and DNAJA3), and a mitochondrial protease (LONP1). However, the putative activity of ABCB10 to export peptides from mitochondria was not lost by ABCB10 depletion. Altogether, these data suggest that ABCB10 is involved in UPR signaling pathway similar to that of HAF-1, although ABCB10 probably does not participate in peptide export from mitochondria.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/genética
Mitocôndrias/metabolismo
Transdução de Sinais/genética
Resposta a Proteínas não Dobradas
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Transportadores de Cassetes de Ligação de ATP/metabolismo
Proteases Dependentes de ATP/genética
Proteases Dependentes de ATP/metabolismo
Chaperonina 60/genética
Chaperonina 60/metabolismo
Perfilação da Expressão Gênica
Glutationa Transferase/genética
Glutationa Transferase/metabolismo
Proteínas de Choque Térmico HSP40/genética
Proteínas de Choque Térmico HSP40/metabolismo
Proteínas de Choque Térmico/genética
Proteínas de Choque Térmico/metabolismo
Células Hep G2
Seres Humanos
Isoenzimas/genética
Isoenzimas/metabolismo
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Oxirredução
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Superóxido Dismutase/genética
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB10 protein, human); 0 (Chaperonin 60); 0 (DNAJA3 protein, human); 0 (HSP40 Heat-Shock Proteins); 0 (HSPD1 protein, human); 0 (Heat-Shock Proteins); 0 (Isoenzymes); 0 (Mitochondrial Proteins); 0 (RNA, Small Interfering); 0 (Reactive Oxygen Species); 0 (SESN3 protein, human); EC 1.15.1.1 (Superoxide Dismutase); EC 1.15.1.1 (superoxide dismutase 2); EC 2.5.1.18 (GSTA1 protein, human); EC 2.5.1.18 (Glutathione Transferase); EC 2.5.1.18 (glutathione S-transferase alpha); EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.21.- (LONP1 protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170320
[St] Status:MEDLINE


  5 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28214511
[Au] Autor:Rampello AJ; Glynn SE
[Ad] Endereço:Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794-5215, USA.
[Ti] Título:Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.
[So] Source:J Mol Biol;429(6):873-885, 2017 Mar 24.
[Is] ISSN:1089-8638
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate.
[Mh] Termos MeSH primário: Proteases Dependentes de ATP/metabolismo
Proteínas de Membrana/metabolismo
Proteínas de Transporte da Membrana Mitocondrial/metabolismo
Proteólise
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/enzimologia
[Mh] Termos MeSH secundário: Dissulfetos
Cinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Disulfides); 0 (Membrane Proteins); 0 (Mitochondrial Membrane Transport Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (TIM10 protein, S cerevisiae); 0 (Tim9 protein, S cerevisiae); EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.21.- (YME1 protein, S cerevisiae)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170220
[St] Status:MEDLINE


  6 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28186560
[Au] Autor:Riar AK; Burstein SR; Palomo GM; Arreguin A; Manfredi G; Germain D
[Ad] Endereço:Department of Medicine, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY 10029, USA.
[Ti] Título:Sex specific activation of the ERα axis of the mitochondrial UPR (UPRmt) in the G93A-SOD1 mouse model of familial ALS.
[So] Source:Hum Mol Genet;26(7):1318-1327, 2017 Apr 01.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The mitochondrial unfolded protein response (UPRmt) is a transcriptional program aimed at restoring proteostasis in mitochondria. Upregulation of mitochondrial matrix proteases and heat shock proteins was initially described. Soon thereafter, a distinct UPRmt induced by misfolded proteins in the mitochondrial intermembrane space (IMS) and mediated by the estrogen receptor alpha (ERα), was found to upregulate the proteasome and the IMS protease OMI. However, the IMS-UPRmt was never studied in a neurodegenerative disease in vivo. Thus, we investigated the IMS-UPRmt in the G93A-SOD1 mouse model of familial ALS, since mutant SOD1 is known to accumulate in the IMS of neural tissue and cause mitochondrial dysfunction. As the ERα is most active in females, we postulated that a differential involvement of the IMS-UPRmt could be linked to the longer lifespan of females in the G93A-SOD1 mouse. We found a significant sex difference in the IMS-UPRmt, because the spinal cords of female, but not male, G93A-SOD1 mice showed elevation of OMI and proteasome activity. Then, using a mouse in which G93A-SOD1 was selectively targeted to the IMS, we demonstrated that the IMS-UPRmt could be specifically initiated by mutant SOD1 localized in the IMS. Furthermore, we showed that, in the absence of ERα, G93A-SOD1 failed to activate OMI and the proteasome, confirming the ERα dependence of the response. Taken together, these results demonstrate the IMS-UPRmt activation in SOD1 familial ALS, and suggest that sex differences in the disease phenotype could be linked to differential activation of the ERα axis of the IMS-UPRmt.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/genética
Receptor alfa de Estrogênio/genética
Mitocôndrias/genética
Superóxido Dismutase/genética
[Mh] Termos MeSH secundário: Proteases Dependentes de ATP/genética
Proteases Dependentes de ATP/metabolismo
Esclerose Amiotrófica Lateral/metabolismo
Esclerose Amiotrófica Lateral/patologia
Animais
Modelos Animais de Doenças
Receptor alfa de Estrogênio/metabolismo
Feminino
Proteínas de Choque Térmico/genética
Serina Peptidase 2 de Requerimento de Alta Temperatura A
Seres Humanos
Masculino
Camundongos
Mitocôndrias/metabolismo
Mitocôndrias/patologia
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Complexo de Endopeptidases do Proteassoma/genética
Complexo de Endopeptidases do Proteassoma/metabolismo
Serina Endopeptidases/genética
Serina Endopeptidases/metabolismo
Caracteres Sexuais
Resposta a Proteínas não Dobradas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Estrogen Receptor alpha); 0 (Heat-Shock Proteins); 0 (Mitochondrial Proteins); EC 1.15.1.1 (SOD1 G93A protein); EC 1.15.1.1 (Superoxide Dismutase); EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.- (mitochondrial intermembrane space protease); EC 3.4.21.108 (HTRA2 protein, human); EC 3.4.21.108 (High-Temperature Requirement A Serine Peptidase 2); EC 3.4.21.108 (Htra2 protein, mouse); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx049


  7 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28085670
[Au] Autor:Bittner LM; Arends J; Narberhaus F
[Ad] Endereço:Microbial Biology, Ruhr University Bochum, Universitätsstr. 150, NDEF 06/783, D-44801 Bochum.
[Ti] Título:When, how and why? Regulated proteolysis by the essential FtsH protease in Escherichia coli.
[So] Source:Biol Chem;398(5-6):625-635, 2017 May 01.
[Is] ISSN:1437-4315
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Cellular proteomes are dynamic and adjusted to permanently changing conditions by ATP-fueled proteolytic machineries. Among the five AAA+ proteases in Escherichia coli FtsH is the only essential and membrane-anchored metalloprotease. FtsH is a homohexamer that uses its ATPase domain to unfold and translocate substrates that are subsequently degraded without the need of ATP in the proteolytic chamber of the protease domain. FtsH eliminates misfolded proteins in the context of general quality control and properly folded proteins for regulatory reasons. Recent trapping approaches have revealed a number of novel FtsH substrates. This review summarizes the substrate diversity of FtsH and presents details on the surprisingly diverse recognition principles of three well-characterized substrates: LpxC, the key enzyme of lipopolysaccharide biosynthesis; RpoH, the alternative heat-shock sigma factor and YfgM, a bifunctional membrane protein implicated in periplasmic chaperone functions and cytoplasmic stress adaptation.
[Mh] Termos MeSH primário: Proteases Dependentes de ATP/metabolismo
Proteínas de Escherichia coli/metabolismo
Escherichia coli/enzimologia
Proteólise
[Mh] Termos MeSH secundário: Proteases Dependentes de ATP/química
Sequência de Aminoácidos
Proteínas de Escherichia coli/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Escherichia coli Proteins); EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.21.- (FtsH protein, E coli)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170114
[St] Status:MEDLINE


  8 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27795298
[Au] Autor:Steen KA; Xu H; Bernlohr DA
[Ad] Endereço:Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
[Ti] Título:FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2.
[So] Source:Mol Cell Biol;37(2), 2017 Jan 15.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue, leading to increased reactive oxygen species (ROS) production and chronic low-grade inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via upregulation of the uncoupling protein 2 (UCP2). Here, we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity and reduces cellular protein sulfhydryl oxidation and, in particular, oxidation of mitochondrial protein cysteine residues. Coincident with the loss of FABP4/aP2 is the upregulation of the antioxidants superoxide dismutase (SOD2), catalase, methionine sulfoxide reductase A, and the 20S proteasome subunits PSMB5 and αß. Reduced mitochondrial protein oxidation in FABP4/aP2 macrophages attenuates the mitochondrial unfolded-protein response (mtUPR) as measured by expression of heat shock protein 60, Clp protease, and Lon peptidase 1. Consistent with a diminished mtUPR, FABP4/aP2 macrophages exhibit reduced expression of cleaved caspase-1 and NLRP3. Secretion of interleukin 1ß (IL-1ß), in response to inflammasome activation, is ablated in FABP4/aP2 macrophages, as well as in FABP4/aP2 inhibitor-treated cells, but partially rescued in FABP4/aP2-null macrophages when UCP2 is silenced. Collectively, these data offer a novel pathway whereby FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2 expression.
[Mh] Termos MeSH primário: Proteínas de Ligação a Ácido Graxo/metabolismo
Inflamassomos/metabolismo
Macrófagos/metabolismo
Proteína Desacopladora 2/metabolismo
[Mh] Termos MeSH secundário: Proteases Dependentes de ATP/metabolismo
Animais
Antioxidantes/metabolismo
Células da Medula Óssea/citologia
Caspase 1/metabolismo
Chaperonina 60/metabolismo
Cisteína/metabolismo
Dieta Hiperlipídica
Deleção de Genes
Homeostase/efeitos dos fármacos
Peróxido de Hidrogênio/farmacologia
Interleucina-1beta/metabolismo
Macrófagos/efeitos dos fármacos
Masculino
Camundongos Endogâmicos C57BL
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
Oxirredução/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Complexo de Endopeptidases do Proteassoma/metabolismo
Subunidades Proteicas/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transdução de Sinais/efeitos dos fármacos
Células Estromais/efeitos dos fármacos
Células Estromais/metabolismo
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Chaperonin 60); 0 (Fabp4 protein, mouse); 0 (Fatty Acid-Binding Proteins); 0 (Inflammasomes); 0 (Interleukin-1beta); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (Nlrp3 protein, mouse); 0 (Protein Subunits); 0 (RNA, Messenger); 0 (Uncoupling Protein 2); BBX060AN9V (Hydrogen Peroxide); EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.22.36 (Caspase 1); EC 3.4.25.1 (Proteasome Endopeptidase Complex); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE


  9 / 734 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26868664
[Au] Autor:Svenstrup K; Nielsen TT; Aidt F; Rostgaard N; Duno M; Wibrand F; Vinther-Jensen T; Law I; Vissing J; Roos P; Hjermind LE; Nielsen JE
[Ad] Endereço:Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
[Ti] Título:SCA28: Novel Mutation in the AFG3L2 Proteolytic Domain Causes a Mild Cerebellar Syndrome with Selective Type-1 Muscle Fiber Atrophy.
[So] Source:Cerebellum;16(1):62-67, 2017 Feb.
[Is] ISSN:1473-4230
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico modelling that this is caused by a novel missense mutation in the AFG3L2 gene. Furthermore, we show, for the first time, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of the brain and selective type I fiber atrophy of skeletal muscle of SCA28 patients indicating non-nervous-system involvement in SCA28 as well.
[Mh] Termos MeSH primário: Proteases Dependentes de ATP/genética
Encéfalo/diagnóstico por imagem
Ataxia Cerebelar/genética
Ataxia Cerebelar/patologia
Fibras Musculares de Contração Lenta/patologia
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: ATPases Associadas a Diversas Atividades Celulares
Adulto
Idoso
Encéfalo/metabolismo
Ataxia Cerebelar/diagnóstico por imagem
Ataxia Cerebelar/metabolismo
Família
Feminino
Seres Humanos
Masculino
Meia-Idade
Fenótipo
Domínios Proteicos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.24.- (AFG3L2 protein, human); EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities)
[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:160213
[St] Status:MEDLINE
[do] DOI:10.1007/s12311-016-0765-1


  10 / 734 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27911893
[Au] Autor:Wang S; Jacquemyn J; Murru S; Martinelli P; Barth E; Langer T; Niessen CM; Rugarli EI
[Ad] Endereço:Institute for Genetics, University of Cologne, Cologne, Germany.
[Ti] Título:The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.
[So] Source:PLoS Genet;12(12):e1006463, 2016 Dec.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.
[Mh] Termos MeSH primário: Proteases Dependentes de ATP/genética
Doenças Desmielinizantes/genética
Cabelo/metabolismo
Metaloendopeptidases/genética
Mitocôndrias/genética
[Mh] Termos MeSH secundário: Proteases Dependentes de ATP/biossíntese
ATPases Associadas a Diversas Atividades Celulares
Animais
Morte Celular/genética
Sobrevivência Celular/genética
Cabelo/crescimento & desenvolvimento
Seres Humanos
Metaloendopeptidases/biossíntese
Camundongos
Mitocôndrias/metabolismo
Mitocôndrias/patologia
Mutação
Bainha de Mielina/metabolismo
Neuroglia/metabolismo
Neurônios/metabolismo
Oligodendroglia/metabolismo
Células de Schwann/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.21.- (ATP-Dependent Proteases); EC 3.4.24.- (Afg3l1 protein, mouse); EC 3.4.24.- (Afg3l2 protein, mouse); EC 3.4.24.- (Metalloendopeptidases); EC 3.4.24.- (m-AAA proteases); EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006463



página 1 de 74 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde