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  1 / 5823 MEDLINE  
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[PMID]:28864542
[Au] Autor:Li C; Götz J
[Ad] Dirección:Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland, Brisbane, Qld, Australia.
[Ti] Título:Somatodendritic accumulation of Tau in Alzheimer's disease is promoted by Fyn-mediated local protein translation.
[So] Fuente:EMBO J;36(21):3120-3138, 2017 Nov 02.
[Is] ISSN:1460-2075
[Cp] País de publicación:England
[La] Idioma:eng
[Ab] Resumen:The cause of protein accumulation in neurodegenerative disease is incompletely understood. In Alzheimer's disease (AD), the axonally enriched protein Tau forms hyperphosphorylated aggregates in the somatodendritic domain. Consequently, a process of subcellular relocalization driven by Tau phosphorylation and detachment from microtubules has been proposed. Here, we reveal an alternative mechanism of protein synthesis of Tau and its hyperphosphorylation in the somatodendritic domain, induced by oligomeric amyloid-ß (Aß) and mediated by the kinase Fyn that activates the ERK/S6 signaling pathway. Activation of this pathway is demonstrated in a range of cellular systems, and in brains from Aß-depositing, Aß-injected, and Fyn-overexpressing mice with Tau accumulation. Both pharmacological inhibition and genetic deletion of Fyn abolish the Aß-induced Tau overexpression via ERK/S6 suppression. Together, these findings present a more cogent mechanism of Tau aggregation in disease. They identify a prominent role for neuronal Fyn in integrating signal transduction pathways that lead to the somatodendritic accumulation of Tau in AD.
[Mh] Términos MeSH primario: Enfermedad de Alzheimer/genética
Precursor de Proteína beta-Amiloide/genética
Neuronas/metabolismo
Biosíntesis de Proteínas
Proteínas Proto-Oncogénicas c-fyn/genética
Proteínas tau/genética
[Mh] Términos MeSH secundario: Enfermedad de Alzheimer/metabolismo
Enfermedad de Alzheimer/patología
Péptidos beta-Amiloides/administración & dosificación
Precursor de Proteína beta-Amiloide/metabolismo
Animales
Embrión de Mamíferos
Regulación de la Expresión Génica
Células HEK293
Hipocampo/metabolismo
Hipocampo/patología
Seres Humanos
Inyecciones Intraventriculares
Sistema de Señalización de MAP Quinasas
Masculino
Ratones
Ratones Consanguíneos C57BL
Ratones Noqueados
Neuronas/patología
Neuronas/ultraestructura
Fragmentos de Péptidos/administración & dosificación
Proteínas Proto-Oncogénicas c-fyn/metabolismo
Puromicina/farmacología
Proteínas Quinasas S6 Ribosómicas/genética
Proteínas Quinasas S6 Ribosómicas/metabolismo
Técnicas Estereotáxicas
Proteínas tau/metabolismo
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Peptide Fragments); 0 (amyloid beta-protein (1-42)); 0 (tau Proteins); 4A6ZS6Q2CL (Puromycin); EC 2.7.10.2 (Fyn protein, mouse); EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn); EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
[Em] Mes de ingreso:1711
[Cu] Fecha actualización por clase:171109
[Lr] Fecha última revisión:171109
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170903
[St] Status:MEDLINE
[do] DOI:10.15252/embj.201797724


  2 / 5823 MEDLINE  
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[PMID]:28803047
[Au] Autor:Singh R; Williams J; Vince R
[Ad] Dirección:Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: singh109@umn.edu.
[Ti] Título:Puromycin based inhibitors of aminopeptidases for the potential treatment of hematologic malignancies.
[So] Fuente:Eur J Med Chem;139:325-336, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicación:France
[La] Idioma:eng
[Ab] Resumen:Substantial progress has been described in the study of puromycin and its analogs for antibiotic properties. However, the peptidase inhibitory activity of related analogs has not been explored as extensively. Specifically, inhibiting aminopeptidases for achieving antitumor effect has been sparsely investigated. Herein, we address this challenge by reporting the synthesis of a series of analogs based on the structural template of puromycin. We also present exhaustive biochemical and in vitro analyses in support of our thesis. Analyzing the structure-activity relationship revealed a steric requirement for maximum potency. Effective inhibitors of Puromycin-Sensitive Aminopeptidase (PSA) are disclosed here. These potential therapeutic agents display superior in vitro antitumor potency against two leukemic cell lines, as compared to known inhibitors of aminopeptidases.
[Mh] Términos MeSH primario: Aminopeptidasas/antagonistas & inhibidores
Antineoplásicos/farmacología
Inhibidores Enzimáticos/farmacología
Neoplasias Hematológicas/tratamiento farmacológico
Puromicina/farmacología
[Mh] Términos MeSH secundario: Aminopeptidasas/metabolismo
Animales
Antineoplásicos/síntesis química
Antineoplásicos/química
Línea Celular Tumoral
Proliferación Celular/efectos de los fármacos
Relación Dosis-Respuesta a Droga
Ensayos de Selección de Medicamentos Antitumorales
Inhibidores Enzimáticos/síntesis química
Inhibidores Enzimáticos/química
Células HL-60
Neoplasias Hematológicas/metabolismo
Neoplasias Hematológicas/patología
Seres Humanos
Estructura Molecular
Puromicina/síntesis química
Puromicina/química
Relación Estructura-Actividad
Células Vero
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); 4A6ZS6Q2CL (Puromycin); EC 3.4.11.- (Aminopeptidases)
[Em] Mes de ingreso:1710
[Cu] Fecha actualización por clase:171018
[Lr] Fecha última revisión:171018
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170814
[St] Status:MEDLINE


  3 / 5823 MEDLINE  
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[PMID]:28779235
[Au] Autor:Zhang QY; Li XD; Liu SQ; Deng CL; Zhang B; Ye HQ
[Ad] Dirección:Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
[Ti] Título:Development of a stable Japanese encephalitis virus replicon cell line for antiviral screening.
[So] Fuente:Arch Virol;162(11):3417-3423, 2017 Nov.
[Is] ISSN:1432-8798
[Cp] País de publicación:Austria
[La] Idioma:eng
[Ab] Resumen:Japanese encephalitis virus (JEV), an important pathogen in Eastern and Southern Asia and the Pacific, has spread to Australia and other territories in recent years. Although the vaccine for JEV has been used in some countries, development of efficient antiviral drugs is still an urgent requirement. Replicon systems have been widely used in the research of viral replication and antiviral screening for West Nile virus (WNV), yellow fever virus (YFV) and dengue virus (DENV). Here, a novel JEV replicon harboring the Rluc and Pac gene (JEV-Pac-Rluc-Rep) was constructed. Furthermore, we established a BHK-21 cell line harboring JEV-Pac-Rluc-Rep (BHK-21 cell line) through continuous puromycin selection. Characterization of cell line stability showed that the replicon RNA could persistently replicate in this cell line for at least up to 10 rounds of passage. Using a known flavivirus inhibitor, the JEV replicon cell line was validated for antiviral screening. The JEV replicon cell line will be a valuable tool for both compound screening and viral replication studies.
[Mh] Términos MeSH primario: Antivirales/uso terapéutico
Virus de la Encefalitis Japonesa (Especie)/fisiología
[Mh] Términos MeSH secundario: Animales
Línea Celular
Cricetinae
Puromicina
Replicón/genética
Replicón/fisiología
Replicación Viral
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Antiviral Agents); 4A6ZS6Q2CL (Puromycin)
[Em] Mes de ingreso:1710
[Cu] Fecha actualización por clase:171025
[Lr] Fecha última revisión:171025
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170806
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3508-9


  4 / 5823 MEDLINE  
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[PMID]:28420111
[Au] Autor:Kho MC; Park JH; Han BH; Tan R; Yoon JJ; Kim HY; Ahn YM; Lee YJ; Kang DG; Lee HS
[Ad] Dirección:Hanbang Body-fluid Research Center, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea. shadowzetx@hanmail.net.
[Ti] Título:Plantago asiatica L. Ameliorates Puromycin Aminonucleoside-Induced Nephrotic Syndrome by Suppressing Inflammation and Apoptosis.
[So] Fuente:Nutrients;9(4), 2017 Apr 14.
[Is] ISSN:2072-6643
[Cp] País de publicación:Switzerland
[La] Idioma:eng
[Ab] Resumen:OBJECTIVE: Nephrotic syndrome, a kidney disease with a variety of causes, is mainly characterized by heavy proteinuria, hypoproteinemia, and ascites. This study was designed to evaluate the underlying mechanism of action of L. (PAL) in treating nephrotic syndrome induced by puromycin aminonucleoside. METHODS: PAL has been used in Asia as a traditional medicine and dietary health supplement. Sprague-Dawley (SD) rats were intravenously injected with puromycin aminonucleoside (75 mg/kg/day), then treated with either Losartan (30 mg/kg/day) or PAL (200 mg/kg/day) by oral gavage for seven days. RESULTS: PAL significantly decreased ascites, proteinuria level, and plasma lipid parameters. In addition, treatment with PAL attenuated histological damage and hypoalbuminemia. Treatment with PAL also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Lower expression levels of the apoptosis markers Bax, caspase-3 and capase-9 were documented in SD rats receiving PAL. PAL also significantly decreased the phosphorylation levels of MAPKs such as ERK, JNK and p38. CONCLUSION: As a multifunctional agent, PAL has a renoprotective effect in nephrotic syndrome rat models. The anti-inflammatory and anti-apoptotic properties, along with reductions in hyperlipidemia and ascites, represent important therapeutic effects. These results indicate that is likely to be a promising agent in the treatment of nephrotic syndrome.
[Mh] Términos MeSH primario: Apoptosis/efectos de los fármacos
Inflamación/prevención & control
Riñón/efectos de los fármacos
Síndrome Nefrótico/tratamiento farmacológico
Extractos Vegetales/farmacología
Plantago
[Mh] Términos MeSH secundario: Animales
Ascitis
Biomarcadores/sangre
Caspasa 3/sangre
Caspasa 9/sangre
Hipoalbuminemia/prevención & control
Inflamación/sangre
Péptidos y Proteínas de Señalización Intracelular/sangre
Riñón/metabolismo
Riñón/patología
Lípidos/sangre
Masculino
Proteínas de la Membrana/sangre
Proteínas Quinasas Activadas por Mitógenos/sangre
Síndrome Nefrótico/inducido químicamente
Síndrome Nefrótico/metabolismo
Síndrome Nefrótico/patología
Fitoterapia
Extractos Vegetales/uso terapéutico
Puromicina Aminonucleósido
Ratas Sprague-Dawley
Proteína X Asociada a bcl-2/sangre
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Biomarkers); 0 (Intracellular Signaling Peptides and Proteins); 0 (Lipids); 0 (Membrane Proteins); 0 (NPHS2 protein); 0 (Plant Extracts); 0 (bcl-2-Associated X Protein); 58-60-6 (Puromycin Aminonucleoside); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 9)
[Em] Mes de ingreso:1709
[Cu] Fecha actualización por clase:170919
[Lr] Fecha última revisión:170919
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170420
[St] Status:MEDLINE


  5 / 5823 MEDLINE  
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[PMID]:28322785
[Au] Autor:Kanungo J
[Ad] Dirección:Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Electronic address: jyotshnabala.kanungo@fda.hhs.gov.
[Ti] Título:Puromycin-resistant lentiviral control shRNA vector, pLKO.1 induces unexpected cellular differentiation of P19 embryonic stem cells.
[So] Fuente:Biochem Biophys Res Commun;486(2):481-485, 2017 Apr 29.
[Is] ISSN:1090-2104
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:RNA silencing is used as a common method for investigating loss-of-function effects of genes of interest. In mammalian cells, RNA interference (RNAi) or RNA silencing can be achieved by transient siRNA (small or short interfering RNA) transfection or by stable shRNA (short hairpin RNA) systems. Various vectors are used for efficient delivery of shRNA. Lentiviral vectors offer an efficient delivery system for stable and long-term expression of the shRNA in mammalian cells. The widely used lentiviral pLKO.1 plasmid vector is very popular in RNAi studies. A large RNAi database, a TRC (the RNAi Consortium) library, was established based on the pLKO.1-TRC plasmid vector. This plasmid (also called pLKO.1-puro) has a puromycin-resistant gene for selection in mammalian cells along with designs for generating lentiviral particles as well for RNA silencing. While using the pLKO.1-puro TRC control shRNA plasmid for transfection in murine P19 embryonic stem (ES) cells, it was unexpectedly discovered that this plasmid vector induced robust endodermal differentiation. Since P19 ES cells are pluripotent and respond to external stimuli that have the potential to alter the phenotype and thus its stemness, other cell types used in RNA silencing studies do not display the obvious effect and therefore, may affect experiments in subtle ways that would go undetected. This study for the first time provides evidence that raises concern and warrants extreme caution while using the pLKO.1-puro control shRNA vector because of its unexpected non-specific effects on cellular integrity.
[Mh] Términos MeSH primario: Endodermo/efectos de los fármacos
Lentivirus/genética
Células Madre Embrionarias de Ratones/efectos de los fármacos
Plásmidos/metabolismo
Puromicina/farmacología
ARN Interferente Pequeño/genética
[Mh] Términos MeSH secundario: Animales
Artefactos
Diferenciación Celular/efectos de los fármacos
Línea Celular
Endodermo/citología
Endodermo/metabolismo
Expresión Génica/efectos de los fármacos
Biblioteca de Genes
Silenciador del Gen
Lentivirus/metabolismo
Ratones
Células Madre Embrionarias de Ratones/citología
Células Madre Embrionarias de Ratones/metabolismo
Plásmidos/química
ARN Interferente Pequeño/metabolismo
Transfección
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (RNA, Small Interfering); 4A6ZS6Q2CL (Puromycin)
[Em] Mes de ingreso:1706
[Cu] Fecha actualización por clase:170608
[Lr] Fecha última revisión:170608
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170322
[St] Status:MEDLINE


  6 / 5823 MEDLINE  
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[PMID]:28314264
[Au] Autor:Bodeau S; Sauzay C; Nyga R; Louandre C; Descamps V; François C; Godin C; Choukroun G; Galmiche A
[Ad] Dirección:Department of Pharmacology and Toxicology, Amiens University Hospital, Amiens, France.
[Ti] Título:Targeting the Unfolded Protein Response as a Potential Therapeutic Strategy in Renal Carcinoma Cells Exposed to Cyclosporine A.
[So] Fuente:Anticancer Res;37(3):1049-1057, 2017 03.
[Is] ISSN:1791-7530
[Cp] País de publicación:Greece
[La] Idioma:eng
[Ab] Resumen:BACKGROUND/AIM: Organ transplant patients treated with the immunosuppressive drug cyclosporine A often present malignant kidney tumors. Cyclosporine A can promote oncogenesis in a cell-intrinsic manner by increasing the production of vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: We explored the impact of cyclosporine A and the role of the unfolded protein response (UPR) on three human renal cell carcinoma (RCC) cell lines under normoxic and hypoxic (1% O ) conditions. RESULTS: Cyclosporine A regulated the expression of VEGF at the post-transcriptional level. Cyclosporine A induced the inositol requiring enzyme-1α (IRE1α) arm of the UPR and stabilized neosynthesized proteins in RCC cells. Toyocamycin, an inhibitor of IRE1α, abolished the clonogenic growth of RCC cells and reduced induction of VEGF by cyclosporine A under hypoxia. CONCLUSION: Our findings highlight the impact of cyclosporine A on the proteostasis of RCC cells, and suggest the potential therapeutic interest of targeting the UPR against tumors arising in the context of organ transplantation.
[Mh] Términos MeSH primario: Carcinoma de Células Renales/metabolismo
Ciclosporina/química
Regulación Neoplásica de la Expresión Génica
Inmunosupresores/química
Neoplasias Renales/metabolismo
Respuesta de Proteína Desplegada
[Mh] Términos MeSH secundario: Línea Celular Tumoral/efectos de los fármacos
Endorribonucleasas/metabolismo
Regulación de la Expresión Génica
Seres Humanos
Hipoxia
Oxígeno/metabolismo
Reacción en Cadena de la Polimerasa
Proteínas Serina-Treonina Quinasas/metabolismo
Puromicina/química
Interferencia de ARN
ARN Interferente Pequeño/metabolismo
Toyocamicina/química
Factor A de Crecimiento Endotelial Vascular/metabolismo
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Immunosuppressive Agents); 0 (RNA, Small Interfering); 0 (VEGFA protein, human); 0 (Vascular Endothelial Growth Factor A); 4A6ZS6Q2CL (Puromycin); 83HN0GTJ6D (Cyclosporine); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 3.1.- (Endoribonucleases); L7995C4D7F (Toyocamycin); S88TT14065 (Oxygen)
[Em] Mes de ingreso:1704
[Cu] Fecha actualización por clase:170411
[Lr] Fecha última revisión:170411
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170319
[St] Status:MEDLINE


  7 / 5823 MEDLINE  
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[PMID]:28259932
[Au] Autor:Wu L; Chen M; Mao H; Wang N; Zhang B; Zhao X; Qian J; Xing C
[Ad] Dirección:Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
[Ti] Título:Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes.
[So] Fuente:Int J Mol Med;39(4):851-860, 2017 Apr.
[Is] ISSN:1791-244X
[Cp] País de publicación:Greece
[La] Idioma:eng
[Ab] Resumen:Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin­methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633­MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid­sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36­fold uptake in receptor­specific cellular delivery in the FcRn­expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co­localization further confirmed that uptake of the nanoconjugates involved receptor­mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633­MP ameliorated puromycin aminonucleoside­induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome.
[Mh] Términos MeSH primario: Portadores de Fármacos
Antígenos de Histocompatibilidad Clase I/metabolismo
Metilprednisolona
Nanopartículas/química
Podocitos/metabolismo
Receptores Fc/metabolismo
Albúmina Sérica Bovina
[Mh] Términos MeSH secundario: Animales
Apoptosis/efectos de los fármacos
Bovinos
Línea Celular Transformada
Portadores de Fármacos/química
Portadores de Fármacos/farmacología
Seres Humanos
Metilprednisolona/química
Metilprednisolona/farmacología
Puromicina Aminonucleósido/efectos adversos
Puromicina Aminonucleósido/farmacología
Albúmina Sérica Bovina/química
Albúmina Sérica Bovina/farmacología
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Drug Carriers); 0 (Fc receptor, neonatal); 0 (Histocompatibility Antigens Class I); 0 (Receptors, Fc); 27432CM55Q (Serum Albumin, Bovine); 58-60-6 (Puromycin Aminonucleoside); X4W7ZR7023 (Methylprednisolone)
[Em] Mes de ingreso:1704
[Cu] Fecha actualización por clase:171116
[Lr] Fecha última revisión:171116
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170306
[St] Status:MEDLINE
[do] DOI:10.3892/ijmm.2017.2902


  8 / 5823 MEDLINE  
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[PMID]:28214366
[Au] Autor:Wu Y; Xu K; Ren C; Li X; Lv H; Han F; Wei Z; Wang X; Zhang Z
[Ad] Dirección:College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
[Ti] Título:Enhanced CRISPR/Cas9-mediated biallelic genome targeting with dual surrogate reporter-integrated donors.
[So] Fuente:FEBS Lett;591(6):903-913, 2017 Mar.
[Is] ISSN:1873-3468
[Cp] País de publicación:England
[La] Idioma:eng
[Ab] Resumen:The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has recently emerged as a simple, yet powerful genome engineering tool, which has been widely used for genome modification in various organisms and cell types. However, screening biallelic genome-modified cells is often time-consuming and technically challenging. In this study, we incorporated two different surrogate reporter cassettes into paired donor plasmids, which were used as both the surrogate reporters and the knock-in donors. By applying our dual surrogate reporter-integrated donor system, we demonstrate high frequency of CRISPR/Cas9-mediated biallelic genome integration in both human HEK293T and porcine PK15 cells (34.09% and 18.18%, respectively). Our work provides a powerful genetic tool for assisting the selection and enrichment of cells with targeted biallelic genome modification.
[Mh] Términos MeSH primario: Sistemas CRISPR-Cas
Edición Génica/métodos
Genoma/genética
Modelos Genéticos
[Mh] Términos MeSH secundario: Alelos
Animales
Secuencia de Bases
Bleomicina/farmacología
Línea Celular
Resistencia a Medicamentos/genética
Citometría de Flujo
Proteínas Fluorescentes Verdes/genética
Proteínas Fluorescentes Verdes/metabolismo
Células HEK293
Seres Humanos
Proteínas Luminiscentes/genética
Proteínas Luminiscentes/metabolismo
Microscopía Fluorescente
Reacción en Cadena de la Polimerasa
Puromicina/farmacología
Reproducibilidad de los Resultados
Porcinos
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Luminescent Proteins); 0 (red fluorescent protein); 11056-06-7 (Bleomycin); 147336-22-9 (Green Fluorescent Proteins); 181494-14-4 (Zeocin); 4A6ZS6Q2CL (Puromycin)
[Em] Mes de ingreso:1706
[Cu] Fecha actualización por clase:170601
[Lr] Fecha última revisión:170601
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170219
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12599


  9 / 5823 MEDLINE  
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[PMID]:28112392
[Au] Autor:Moriyama T; Sasaki K; Karasawa K; Uchida K; Nitta K
[Ad] Dirección:Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
[Ti] Título:Intracellular transcytosis of albumin in glomerular endothelial cells after endocytosis through caveolae.
[So] Fuente:J Cell Physiol;232(12):3565-3573, 2017 Dec.
[Is] ISSN:1097-4652
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:We previously described albumin endocytosis through caveolae in human renal glomerular endothelial cells (HRGECs). This suggested a new albumin transcytosis pathway, in addition to the fenestral pathway. As a next step, we investigated albumin transcytosis in HRGECs after caveolar endocytosis. HRGECs were incubated with Alexa Fluor 488-labeled bovine serum albumin from 0 to 360 min. Next, markers for endosomes, endoplasmic reticulum (ER), golgi apparatus (GA), lysosomes, and proteasomes and Fc receptors, microtubules, and actin were monitored by immunofluorescence. Labeled albumin co-localization with endosomes was gradually and significantly increased and it was significantly higher than with the other markers at any timepoint. Albumin, placed on inside of the Transwell membrane, diffused through HRGEC monolayers during a 360 min incubation period. This transportation of albumin through HRGECs was inhibited by methyl beta cyclodextrin (MBCD), a caveolae disrupting agent. MBCD also decreased albuminuria, causing decreased caveolin-1 (Cav-1) expression on glomerular capillaries, in puromycin aminonucleoside induced nephrotic mice. Albumin transcytosis depends on early endosomes, but not on other organelles, Fc receptors, or cytoskeletal components. Caveolae disruption prevented albumin transportation through HRGECs and decreased albuminuria in nephrotic mice. This newly described caveolae-dependent albumin pathway through glomerular endothelial cells is a potential pathogenetic mechanism for albuminuria, independent of the fenestrae.
[Mh] Términos MeSH primario: Albuminuria/metabolismo
Caveolas/metabolismo
Endocitosis
Endosomas/metabolismo
Células Endoteliales/metabolismo
Glomérulos Renales/irrigación sanguínea
Albúmina Sérica Bovina/metabolismo
Transcitosis
[Mh] Términos MeSH secundario: Albuminuria/inducido químicamente
Albuminuria/prevención & control
Animales
Caveolas/efectos de los fármacos
Caveolina 1/metabolismo
Células Cultivadas
Modelos Animales de Enfermedad
Endocitosis/efectos de los fármacos
Endosomas/efectos de los fármacos
Células Endoteliales/efectos de los fármacos
Seres Humanos
Masculino
Ratones Consanguíneos C57BL
Nefrosis/inducido químicamente
Nefrosis/metabolismo
Puromicina Aminonucleósido
Factores de Tiempo
Transcitosis/efectos de los fármacos
beta-Ciclodextrinas/farmacología
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Cav1 protein, mouse); 0 (Caveolin 1); 0 (beta-Cyclodextrins); 0 (methyl-beta-cyclodextrin); 27432CM55Q (Serum Albumin, Bovine); 58-60-6 (Puromycin Aminonucleoside)
[Em] Mes de ingreso:1710
[Cu] Fecha actualización por clase:171116
[Lr] Fecha última revisión:171116
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170124
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25817


  10 / 5823 MEDLINE  
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[PMID]:28102767
[Au] Autor:Carter J; Weaver BA; Chiacchio MA; Messersmith AR; Lynch WE; Feske BD; Gumina G
[Ad] Dirección:a Department of Pharmaceutical and Administrative Sciences , Presbyterian College School of Pharmacy , Clinton , SC , USA.
[Ti] Título:Synthesis, stereochemical characterization, and antimicrobial evaluation of a potentially nonnephrotoxic 3'-C-acethydrazide puromycin analog.
[So] Fuente:Nucleosides Nucleotides Nucleic Acids;36(3):224-241, 2017 Mar 04.
[Is] ISSN:1532-2335
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3'-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 µM concentration.
[Mh] Términos MeSH primario: Antibacterianos/química
Antibacterianos/farmacología
Puromicina/química
[Mh] Términos MeSH secundario: Antibacterianos/síntesis química
Técnicas de Química Sintética
Cristalografía por Rayos X
Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos
Pruebas de Sensibilidad Microbiana
Puromicina/efectos adversos
Puromicina/farmacología
Staphylococcus aureus/efectos de los fármacos
Staphylococcus epidermidis/efectos de los fármacos
Estereoisomerismo
Relación Estructura-Actividad
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Nm] Nombre de substancia:
0 (Anti-Bacterial Agents); 4A6ZS6Q2CL (Puromycin)
[Em] Mes de ingreso:1703
[Cu] Fecha actualización por clase:170303
[Lr] Fecha última revisión:170303
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:170120
[St] Status:MEDLINE
[do] DOI:10.1080/15257770.2016.1264590



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