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1.
Biol. Res ; 48: 1-11, 2015. ilus, graf, tab
Article in English | LILACS | ID: biblio-950803

ABSTRACT

BACKGROUND: A highly regulated trafficking of cargo vesicles in eukaryotes performs protein delivery to a variety of cellular compartments of endomembrane system. The two main routes, the secretory and the endocytic pathways have pivotal functions in uni- and multi-cellular organisms. Protein delivery and targeting includes cargo recognition, vesicle formation and fusion. Developing new tools to modulate protein trafficking allows better understanding the endomembrane system mechanisms and their regulation. The compound Sortin2 has been described as a protein trafficking modulator affecting targeting of the vacuolar protein carboxypeptidase Y (CPY), triggering its secretion in Saccharomyces cerevisiae. RESULTS: A reverse chemical-genetics approach was used to identify key proteins for Sortin2 bioactivity. A genome-wide Sortin2 resistance screen revealed six yeast deletion mutants that do not secrete CPY when grown at Sortin2 condition where the parental strain does: met18, sla1, clc1, dfg10, dpl1 and yjl175w. Integrating mutant phenotype and gene ontology annotation of the corresponding genes and their interactome pointed towards a high representation of genes involved in the endocytic process. In wild type yeast endocytosis towards the vacuole was faster in presence of Sortin2, which further validates the data of the genome-wide screen. This effect of Sortin2 depends on structural features of the molecule, suggesting compound specificity. Sortin2 did not affect endocytic trafficking in Sortin2-resistant mutants, strongly suggesting that the Sortin2 effects on the secretory and endocytic pathways are linked. CONCLUSIONS: Overall, the results reveal that Sortin2 enhances the endocytic transport pathway in Saccharomyces cerevisiae. This cellular effect is most likely at the level where secretory and endocytic pathways are merged. Them Sortin2 specificity over the endomembrane system places it as a powerful biological modulator for cell biology.


Subject(s)
Plant Proteins/physiology , Rhodanine/analogs & derivatives , Saccharomyces cerevisiae/metabolism , Vacuoles/metabolism , Alkanesulfonates/pharmacology , Protein Transport/genetics , Endocytosis/physiology , Phenotype , Rhodanine/pharmacology , Vacuoles/physiology , Biological Transport , Secretory Pathway
2.
Salud pública Méx ; 56(4): 333-347, jul.-ago. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-733312

ABSTRACT

Objetivo. Corregir la mala clasificación y mejorar la calidad de la información sobre la mortalidad materna en México. Material y métodos. A través de los registros clínicos y autopsias verbales, se estudiaron todas las defunciones certificadas como maternas y una selección de defunciones de mujeres en edad fértil, cuyas causas fueron consideradas como sospechosas de encubrir una muerte materna; todas ocurridas durante 2011 en México. Resultados. La búsqueda intencionada y reclasificación de muertes maternas permitió rescatar más de 100 muertes que no habían sido registradas ni codificadas inicialmente como maternas y se ratificaron o rectificaron las causas anotadas en los certificados de defunción. Este procedimiento también permitió reclasificar como muertes maternas 297 defunciones de la base preliminar del Instituto Nacional de Estadística y Geografía. Conclusiones. La Búsqueda Intencionada y Reclasificación de Muertes Maternas es un procedimiento muy útil para mejorar la calidad de la información sobre la mortalidad materna.


Objective. To correct the misclassification and improve the quality of information on maternal mortality in Mexico. Materials and methods. Using clinical records and verbal autopsies, we studied all deaths certified as maternal deaths as well as a selection of deaths of women of childbearing age whose causes were considered as suspected of hiding a maternal death, all of which occurred during 2011 within Mexico. Results. The deliberate search of maternal deaths and reclassification allowed the rescue of just over 100 deaths that were not originally registered or coded as maternal and confirmed or corrected the causes of death recorded on death certificates as confirmed maternal deaths. This procedure also allowed the reclassification of 297 maternal deaths of women in the groundwork of the National Institute of Statistics and Geography. Conclusions. International Search and Reclassification of Maternal Deaths is a very useful procedure for improving the classification of cases that were not classified as maternal deaths and the effect was greater with the coding of indirect obstetric deaths.


Subject(s)
Chlorophenols/metabolism , Euryarchaeota/metabolism , Pentachlorophenol/metabolism , Anaerobiosis , Alkanesulfonates/metabolism , Biodegradation, Environmental , Bacteria, Anaerobic/metabolism , Chlorides/metabolism , Models, Chemical , Molybdenum
3.
Article in Chinese | WPRIM | ID: wpr-300214

ABSTRACT

To investigate formation mechanism of secologanic acid sulfonates in sulfur-fumigated buds of Lonicera japonica, secologanic acid was enriched and purified from the sun-dried buds of L. japonica by various column chromatography on macroporus resin HPD-100, silica gel and ODS. The stimulation experiments of sulfur-fumigation process were carried out using secologanic acid reacted with SO2 in the aqueous solution. The reaction mechanism could be involved in the esterification or addition reaction. The present investigation provides substantial evidences for interpreting formation pathway of secologanic acid sulfonates in sulfur-fumigated buds of L. japonica.


Subject(s)
Alkanesulfonates , Chemistry , Carboxylic Acids , Chemistry , Chromatography, High Pressure Liquid , Flowers , Chemistry , Lonicera , Chemistry , Models, Chemical , Molecular Structure , Sulfur , Chemistry , Pharmacology , Sulfur Dioxide , Chemistry , Water , Chemistry
4.
Chinese Journal of Cardiology ; (12): 143-149, 2013.
Article in Chinese | WPRIM | ID: wpr-292010

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of peroxisome proliferator-activated receptor (PPAR) α/γ agonist on atherosclerotic plaque stabilization in diabetic LDL receptor knockout (LDLr-/-) mice.</p><p><b>METHODS</b>Female 4-week-old LDLr-/- mice fed with high-glucose and high-fat diet for 4 weeks were randomly divided into three groups (n = 15 each): control group (only fed with high-glucose and high-fat diet), diabetic group [induced by high-glucose and high-fat diet combined with a low-dose of streptozotocin (STZ)] without tesaglitazar and with tesaglitazar (20 µg/kg oral treatment). After 6 weeks, the mice were sacrificed, body weight, fasting blood glucose (Glu), total cholesterol (TC), triglyceride (TG) levels were measured. The expression of ICAM-1, VCAM-1, MCP-1 in the brachiocephalic atherosclerotic lesions were determined by Western blot and immunohistochemistry, respectively. Brachiocephalic artery was prepared for morphologic study (HE, oil red O, Sirius red staining) and immunohistochemical analysis (macrophage surface molecule-3, α-smooth muscle actin), respectively.</p><p><b>RESULTS</b>Serum TC [(32.34 ± 3.26) mmol/L vs. (16.17 ± 1.91) mmol/L], TG [(3.57 ± 0.99) mmol/L vs. (2.21 ± 0.11) mmol/L] and Glu [(15.21 ± 4.67) mmol/L vs. (6.89 ± 0.83) mmol/L] levels were significantly higher in diabetic group than in the control group (all P < 0.01). The expression of ICAM-1 (2.31 ± 0.35 vs.1.34 ± 0.21), VCAM-1 (1.65 ± 0.14 vs.0.82 ± 0.26), MCP-1 (2.27 ± 0.16 vs.1.56 ± 0.23) were significantly upregulated in diabetic group compared with control group (all P < 0.01). Brachiocephalic atherosclerotic plaque area [(4.597 ± 1.260)×10(3) µm(2) vs. (0.075 ± 0.030)×10(3) µm(2)], lipid deposition [(47.23 ± 2.64)% vs. (9.67 ± 1.75)%], Mac-3 positive area [(19.15 ± 3.51)% vs. (1.72 ± 0.16)%], α-smooth muscle actin [(5.54 ± 1.17)% vs. (2.13 ± 0.41)%] and collagen content [(4.27 ± 0.74)% vs. (0.43 ± 0.09)%] were all significantly larger/higher in diabetic LDLr-/- mice than in the control group (all P < 0.01). While tesaglitazar treatment significantly reduced serum TC [(30.47 ± 3.18) mmol/L], TG [(3.14 ± 0.71) mmol/L] and Glu [(7.92 ± 1.28) mmol/L] levels (all P < 0.01). Similarly, the expression of ICAM-1 [(1.84 ± 0.22)], VCAM-1 [(1.27 ± 0.11)], MCP-1 [(1.83 ± 0.24)], brachiocephalic atherosclerotic lesion area[(1.283 ± 0.410)×10(3) µm(2)], lipid deposition[(23.52 ± 1.39)%] were also significantly reduced by tesaglitazar (all P < 0.05). Moreover, tesaglitazar increased α-smooth muscle actin [(9.46 ± 1.47)%] and collagen content [(6.32 ± 1.15)%] in diabetic LDLr-/- mice (all P < 0.05). In addition, lipid deposition and Mac-3 positive areas [(10.67 ± 0.88)% vs. (15.83 ± 1.01)%] in the aortic root were also reduced in tesaglitazar treated diabetic LDLr-/- mice (P < 0.01).</p><p><b>CONCLUSIONS</b>Tesaglitazar has anti-inflammatory effects in the diabetic LDLr-/- mice. Tesaglitazar could reduce lipid deposition, increase collagen and α-SMA content in the brachiocephalic atherosclerotic lesions, thus, stabilize atherosclerotic plaque in this model.</p>


Subject(s)
Actins , Metabolism , Alkanesulfonates , Pharmacology , Animals , Collagen , Metabolism , Diabetes Mellitus, Experimental , Metabolism , Pathology , Diet, High-Fat , Female , Intercellular Adhesion Molecule-1 , Metabolism , Lipid Metabolism , Mice , Mice, Knockout , PPAR alpha , PPAR gamma , Phenylpropionates , Pharmacology , Plaque, Atherosclerotic , Metabolism , Pathology , Receptors, LDL , Genetics , Vascular Cell Adhesion Molecule-1 , Metabolism
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