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  1 / 2025 MEDLINE  
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[PMID]:28456517
[Au] Autor:Klein-Szanto AJ; Bassi DE
[Ad] Endereço:Fox Chase Cancer Center, 333 Cotman Ave, Philadelphia 19111, USA.
[Ti] Título:Proprotein convertase inhibition: Paralyzing the cell's master switches.
[So] Source:Biochem Pharmacol;140:8-15, 2017 09 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Proprotein convertases are serine proteases responsible for the cleavage and subsequent activation of protein substrates, many of them relevant for the development of an ample variety of diseases. Seven of the PCs, including furin and PACE4, recognize and hydrolyze the C-terminal end of the general sequence RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some systems, PC-mediated substrate activation results in the development of pathological processes, such as cancer, endocrinopathies, and cardiovascular and infectious diseases. After establishing PCs as relevant contributors to disease processes, research efforts were directed towards the development of inhibition strategies, including small and large molecules, anti-sense therapies, and antibody-based therapies. Most of these inhibitors mimic the consensus sequence of PCs, blocking the active site in a competitive manner. The most promising inhibitors were designed as bioengineered proteins; however, some non-protein and peptidomimetic agents have also proved to be effective. These efforts led to the design of pre-clinical studies and clinical trials utilizing inhibitors to PCs. Although the initial studies were performed using non-selective PCs inhibitors, such as CMK, the search for more specific, and compartmentalized selective inhibitors resulted in specific activities ascribed to some, but not all of the PCs. For instance, PACE4 inhibitors were effective in decreasing prostate cancer cell proliferation, and neovascularization. Decreased metastatic ovarian cancer utilizing furin inhibitors represents one of the major endeavors, currently in a phase II trial stage. Antibodies targeting PCSK-9 decreased significantly the levels of HDL-cholesterol, in a phase III trial. The study of Proprotein convertases has reached a stage of maturity. New strategies based on the alteration of their activity at the cellular and clinical level represent a promising experimental pharmacology field. The development of allosteric inhibitors, or specific agents directed against individual PCs is one of the challenges to be unraveled in the future.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Desenho de Drogas
Drogas em Investigação/uso terapêutico
Inibidores Enzimáticos/uso terapêutico
Terapia de Alvo Molecular
Neoplasias/tratamento farmacológico
Pró-Proteína Convertases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Ativação Metabólica
Animais
Antineoplásicos/química
Antineoplásicos/farmacocinética
Antineoplásicos/farmacologia
Sítios de Ligação
Ligação Competitiva
Domínio Catalítico
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Drogas em Investigação/química
Drogas em Investigação/farmacocinética
Drogas em Investigação/farmacologia
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacocinética
Inibidores Enzimáticos/farmacologia
Seres Humanos
Isoenzimas/antagonistas & inibidores
Isoenzimas/química
Isoenzimas/metabolismo
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/química
Proteínas de Neoplasias/metabolismo
Neoplasias/enzimologia
Neoplasias/patologia
Pró-Fármacos/química
Pró-Fármacos/farmacocinética
Pró-Fármacos/farmacologia
Pró-Fármacos/uso terapêutico
Pró-Proteína Convertases/química
Pró-Proteína Convertases/metabolismo
Carga Tumoral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drugs, Investigational); 0 (Enzyme Inhibitors); 0 (Isoenzymes); 0 (Neoplasm Proteins); 0 (Prodrugs); EC 3.4.21.- (Proprotein Convertases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  2 / 2025 MEDLINE  
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[PMID]:28468828
[Au] Autor:Essalmani R; Susan-Resiga D; Guillemot J; Kim W; Sachan V; Awan Z; Chamberland A; Asselin MC; Ly K; Desjardins R; Day R; Prat A; Seidah NG
[Ad] Endereço:From the Laboratories of Biochemical Neuroendocrinology, Institut de Recherches Cliniques de Montréal, University of Montreal, Montreal, Quebec H2W 1R7, Canada and.
[Ti] Título:Thrombin activation of protein C requires prior processing by a liver proprotein convertase.
[So] Source:J Biol Chem;292(25):10564-10573, 2017 06 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein C, a secretory vitamin K-dependent anticoagulant serine protease, inactivates factors Va/VIIIa. It is exclusively synthesized in liver hepatocytes as an inactive zymogen (proprotein C). In humans, thrombin cleavage of the propeptide at PR ↓ results in activated protein C (APC; residues 222-461). However, the propeptide is also cleaved by a furin-like proprotein convertase(s) (PCs) at K SHL ↓ (underlined basic residues critical for the recognition by PCs), but the order of cleavage is unknown. Herein, we present evidence that at the surface of COS-1 cells, mouse proprotein C is first cleaved by the convertases furin, PC5/6A, and PACE4. In mice, this cleavage occurs at the equivalent site, K KIL ↓, and requires the presence of Arg at P1 and a combination of two other basic residues at either P2 (Lys ), P6 (Arg ), or P8 (Lys ) positions. Notably, the thrombin-resistant R221A mutant is still cleaved by these PCs, revealing that convertase cleavage can precede thrombin activation. This conclusion was supported by the fact that the APC-specific activity in the medium of COS-1 cells is exclusively dependent on prior cleavage by the convertases, because both R198A and R221A lack protein C activity. Primary cultures of hepatocytes derived from wild-type or hepatocyte-specific furin, PC5/6, or complete PACE4 knock-out mice suggested that the cleavage of overexpressed proprotein C is predominantly performed by furin intracellularly and by all three proprotein convertases at the cell surface. Indeed, plasma analyses of single-proprotein convertase-knock-out mice showed that loss of the convertase furin or PC5/6 in hepatocytes results in a ∼30% decrease in APC levels, with no significant contribution from PACE4. We conclude that prior convertase cleavage of protein C in hepatocytes is critical for its thrombin activation.
[Mh] Termos MeSH primário: Hepatócitos/enzimologia
Fígado/enzimologia
Pró-Proteína Convertase 5/metabolismo
Proteína C/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Células COS
Cercopithecus aethiops
Ativação Enzimática/fisiologia
Células Hep G2
Seres Humanos
Camundongos
Camundongos Knockout
Mutação de Sentido Incorreto
Pró-Proteína Convertase 5/genética
Pró-Proteína Convertases/genética
Pró-Proteína Convertases/metabolismo
Proteína C/genética
Serina Endopeptidases/genética
Serina Endopeptidases/metabolismo
Trombina/genética
Trombina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protein C); EC 3.4.21.- (PCSK6 protein, human); EC 3.4.21.- (Pcsk6 protein, mouse); EC 3.4.21.- (Proprotein Convertase 5); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.770040


  3 / 2025 MEDLINE  
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[PMID]:28846083
[Au] Autor:Rapti G; Li C; Shan A; Lu Y; Shaham S
[Ad] Endereço:Laboratory of Developmental Genetics, The Rockefeller University, New York, New York, USA.
[Ti] Título:Glia initiate brain assembly through noncanonical Chimaerin-Furin axon guidance in C. elegans.
[So] Source:Nat Neurosci;20(10):1350-1360, 2017 Oct.
[Is] ISSN:1546-1726
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a Chimaerin (CHIN-1)- Furin (KPC-1) double-mutant that severely disrupts assembly. CHIN-1 and KPC-1 function noncanonically, in glia and pioneer neurons, for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo (CELSR) in follower-axon navigation. Taken together, our studies reveal previously undescribed glial roles in pioneer-axon guidance, suggesting conserved principles of brain assembly.
[Mh] Termos MeSH primário: Orientação de Axônios/fisiologia
Encéfalo/crescimento & desenvolvimento
Proteínas de Caenorhabditis elegans/fisiologia
Caenorhabditis elegans/fisiologia
Proteínas Ativadoras de GTPase/fisiologia
Neuroglia/fisiologia
Pró-Proteína Convertases/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Encéfalo/ultraestrutura
Proteínas de Caenorhabditis elegans/genética
Proteínas Ativadoras de GTPase/genética
Mutação
Proteínas do Tecido Nervoso/fisiologia
Netrinas
Neuroglia/ultraestrutura
Neurônios/fisiologia
Pró-Proteína Convertases/genética
Semaforinas/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CHIN-1 protein, C elegans); 0 (Caenorhabditis elegans Proteins); 0 (GTPase-Activating Proteins); 0 (Nerve Tissue Proteins); 0 (Netrins); 0 (Semaphorins); 0 (UNC-6 protein, C elegans); EC 3.4.21.- (KPC-1 protein, C elegans); EC 3.4.21.- (Proprotein Convertases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1038/nn.4630


  4 / 2025 MEDLINE  
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[PMID]:28829851
[Au] Autor:Mark DB; Schulman KA
[Ad] Endereço:Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
[Ti] Título:PCSK9 Inhibitors and the Choice Between Innovation, Efficiency, and Affordability.
[So] Source:JAMA;318(8):711-712, 2017 08 22.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: LDL-Colesterol
Pró-Proteína Convertases
[Mh] Termos MeSH secundário: Seres Humanos
Serina Endopeptidases
[Pt] Tipo de publicação:EDITORIAL; COMMENT
[Nm] Nome de substância:
0 (Cholesterol, LDL); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Serine Endopeptidases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.8907


  5 / 2025 MEDLINE  
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[PMID]:28739196
[Au] Autor:Underberg JA; Blaha MJ; Jackson EJ; Jones PH
[Ad] Endereço:NYU School of Medicine, NYU Center for Prevention of Cardiovascular Disease, Bellevue Hospital Lipid Clinic, National Lipid Association, New York, NY.
[Ti] Título:Developing Optimized Treatment Plans for Patients with Dyslipidemia in the Era of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapeutics.
[So] Source:Am J Med;130(10):1233, 2017 Oct.
[Is] ISSN:1555-7162
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This educational content was derived from a live satellite symposium at the American College of Physicians Internal Medicine Meeting 2017 in San Diego, California (online at http://courses.elseviercme.com/acp/702e). This activity will focus on optimized treatment plans for patients with dyslipidemia in the era of proprotein convertase subtilisin/kexin type 9 inhibitor therapeutics. Low-density lipoprotein cholesterol has been identified as an important therapeutic target to prevent the progression of atherosclerotic disease; however, only 1 of every 3 adults with high low-density lipoprotein cholesterol has the condition under control. Expert faculty on this panel will discuss the science of proprotein convertase subtilisin/kexin type 9 inhibitors and aid physicians in the best practices to achieve low-density lipoprotein cholesterol target in their patients.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Dislipidemias/tratamento farmacológico
Planejamento de Assistência ao Paciente
Pró-Proteína Convertases/antagonistas & inibidores
[Mh] Termos MeSH secundário: LDL-Colesterol/sangue
Seres Humanos
[Pt] Tipo de publicação:INTERACTIVE TUTORIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Cholesterol, LDL); EC 3.4.21.- (Proprotein Convertases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  6 / 2025 MEDLINE  
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[PMID]:28722823
[Au] Autor:Dianati V; Shamloo A; Kwiatkowska A; Desjardins R; Soldera A; Day R; Dory YL
[Ad] Endereço:Institut de Pharmacologie de Sherbrooke, IPS, Département de Chimie, Faculté des Sciences, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Québec, J1H 5N4, Canada.
[Ti] Título:Rational Design of a Highly Potent and Selective Peptide Inhibitor of PACE4 by Salt Bridge Interaction with D160 at Position P3.
[So] Source:ChemMedChem;12(15):1169-1172, 2017 Aug 08.
[Is] ISSN:1860-7187
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal. Moreover, the ß-branched nature of the new P3 residue favors the extended ß-sheet conformation usually associated with substrates of proteases. This work provides new insight for better understanding of ß-sheet backbone-backbone interactions between serine proteases and their peptidic ligands.
[Mh] Termos MeSH primário: Desenho de Drogas
Peptídeos/farmacologia
Pró-Proteína Convertases/antagonistas & inibidores
Inibidores de Serino Proteinase/farmacologia
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Peptídeos/síntese química
Peptídeos/química
Pró-Proteína Convertases/metabolismo
Sais/síntese química
Sais/química
Sais/farmacologia
Serina Endopeptidases/metabolismo
Inibidores de Serino Proteinase/síntese química
Inibidores de Serino Proteinase/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 0 (Salts); 0 (Serine Proteinase Inhibitors); EC 3.4.21.- (PCSK6 protein, human); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Serine Endopeptidases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1002/cmdc.201700300


  7 / 2025 MEDLINE  
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[PMID]:28645614
[Au] Autor:Caruana BT; Skoric A; Brown AJ; Lutze-Mann LH
[Ad] Endereço:School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Australia. Electronic address: b.caruana@unsw.edu.au.
[Ti] Título:Site-1 protease, a novel metabolic target for glioblastoma.
[So] Source:Biochem Biophys Res Commun;490(3):760-766, 2017 Aug 26.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sterol regulatory element binding proteins (SREBPs) are transcriptional regulators of lipids which promote glioblastoma growth. Here, we investigate the effect of inhibiting expression of SREBP target genes in human glioblastoma cells. This was achieved by using PF-429242 to inhibit site-1 protease (S1P), an enzyme required for SREBP activation. Treatment with PF-429242 decreased glioblastoma cell viability, induced apoptosis and downregulated steroid, isoprenoid and unsaturated fatty acid biosynthetic pathways. Several pro-inflammatory genes were upregulated. Collectively, these results demonstrate the potential of S1P as a target for glioblastoma therapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Proliferação Celular/efeitos dos fármacos
Glioblastoma/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Pró-Proteína Convertases/antagonistas & inibidores
Pirrolidinas/farmacologia
Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Colesterol/metabolismo
Cricetulus
Inibidores Enzimáticos/farmacologia
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Glioblastoma/genética
Glioblastoma/patologia
Seres Humanos
Terapia de Alvo Molecular
Pró-Proteína Convertases/metabolismo
Serina Endopeptidases/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); 0 (PF-429242); 0 (Pyrrolidines); 0 (SREBF2 protein, human); 0 (Sterol Regulatory Element Binding Protein 2); 0 (Sterol Regulatory Element Binding Proteins); 97C5T2UQ7J (Cholesterol); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.112 (membrane-bound transcription factor peptidase, site 1)
[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:170625
[St] Status:MEDLINE


  8 / 2025 MEDLINE  
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[PMID]:28579602
[Au] Autor:Ishii H; Murohara T
[Ad] Endereço:Department of Cardiology, Nagoya University Graduate School of Medicine.
[Ti] Título:Lipid-Lowering Therapy With Monoclonal Antibodies to Proprotein Convertase Subtilisin-Kexin Type 9 - Lessons From Recent Clinical Trials.
[So] Source:Circ J;81(10):1386-1387, 2017 09 25.
[Is] ISSN:1347-4820
[Cp] País de publicação:Japan
[La] Idioma:eng
[Mh] Termos MeSH primário: Anticorpos Monoclonais
Pró-Proteína Convertases/imunologia
[Mh] Termos MeSH secundário: LDL-Colesterol
Seres Humanos
Lipídeos
Pró-Proteína Convertase 9
Serina Endopeptidases/imunologia
Subtilisinas
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Cholesterol, LDL); 0 (Lipids); EC 3.4.21.- (Proprotein Convertase 9); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.- (Subtilisins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1253/circj.CJ-17-0511


  9 / 2025 MEDLINE  
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[PMID]:28511335
[Au] Autor:Wu NQ; Li JJ
[Ti] Título:[Gene mutations of proprotein convertase subtilisin/kexin type 9 and low density lipoprotein-cholesterol].
[So] Source:Zhonghua Xin Xue Guan Bing Za Zhi;45(5):444-446, 2017 May 24.
[Is] ISSN:0253-3758
[Cp] País de publicação:China
[La] Idioma:chi
[Mh] Termos MeSH primário: LDL-Colesterol
Mutação
Pró-Proteína Convertase 9/genética
[Mh] Termos MeSH secundário: Seres Humanos
Pró-Proteína Convertases
Subtilisinas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholesterol, LDL); EC 3.4.21.- (Proprotein Convertase 9); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Subtilisins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0253-3758.2017.05.018


  10 / 2025 MEDLINE  
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[PMID]:28511328
[Au] Autor:Yang XQ; Yu Y; Guo SD; Cui YJ; Hu GL; Feng L; Wang DX; Qin SC
[Ad] Endereço:Department of Cardiology, Second Xiangya Hospital of Central South University, Changsha 410011, China.
[Ti] Título:[Effects of apolipoprotein E deficiency on sphingosine-1-phosphate distribution in plasma and lipoproteins of mice].
[So] Source:Zhonghua Xin Xue Guan Bing Za Zhi;45(5):419-426, 2017 May 24.
[Is] ISSN:0253-3758
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the effects of apolipoprotein E deficiency (Apo E(-/-)) on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice. Five male or female Apo E(-/-) or wild type (WT) mice were fed with chow diet and sacrificed at 32-week-age and plasma was collected. The constituents of lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein concentration of constituents was detected by BCA protein quantitative kit, and the S1P concentration in plasma and various lipoprotein constituents was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot was used to determine the plasma, liver, and kidney protein expression of apolipoprotein M(Apo M), which is considered as specific ligand of S1P.The S1P concentration in plasma and various constituents of lipoprotein in the Apo E(-/-) mice was compared to respective WT mice. (1)Plasma S1P content was significantly higher in the Apo E(-/-) groups than that of WT groups (male: (535.7±78.5)nmol/L vs. (263.3±22.0)nmol/L; female: (601.1±64.0)nmol/L vs. (279.0±33.9)nmol/L; all <0.01). (2) Compared with WT mice, S1P content in non-HDL(LDL+ VLDL) was significantly higher in Apo E(-/-) mice (male: (504.9±52.8)nmol/L vs. (28.7±9.0)nmol/L; female: (427.7±27.4) vs. (27.8±4.7)nmol/L; after standardization of protein concentration, male: (385.0±41.2)pmol/mg protein vs. (71.4±6.6)pmol/mg protein; female: (330.2±22.0)pmol/mg protein vs. (67.2±12.1)pmol/mg protein; all <0.01). (3) The expression of Apo M in plasma, liver and kidney was significantly higher in Apo E(-/-) groups than that of WT groups(all <0.05). The deficiency of Apo E could lead to upregulated S1P expression in the non-HDL, the underlying mechanism might be the increased transfer of HDL into the non-HDL by Apo M-S1P.
[Mh] Termos MeSH primário: Apolipoproteínas E
Lipoproteínas HDL
Lipoproteínas LDL
Pró-Proteína Convertases
Serina Endopeptidases
[Mh] Termos MeSH secundário: Animais
Feminino
Fígado
Masculino
Camundongos
Espectrometria de Massas em Tandem
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoproteins E); 0 (Lipoproteins, HDL); 0 (Lipoproteins, LDL); EC 3.4.21.- (Proprotein Convertases); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.112 (membrane-bound transcription factor peptidase, site 1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0253-3758.2017.05.011



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