Participación de rafts en enfermedades neurológicas / Role of rafts in neurological disorders

Introducción: Los rafts constituyen nano-dominios estructurales de naturaleza lipoproteica que propician la eficiente transducción de señales y la modulación de procesos fisiológicos asociados a la membrana plasmática. En el sistema nervioso, la alteración de estos dominios se ha asociado con el desarrollo de diversos padecimientos. Desarrollo: En el presente artículo se revisa el concepto de rafts, los procesos del sistema nervioso en los cuales están involucrados y su papel en distintas afectaciones, entre las que se destacan las enfermedades de Parkinson, Alzheimer y Huntington. Conclusiones: Dadas las evidencias de su participación en diversas neuropatologías, la preservación y/o reconstitución de los rafts se vislumbran como una atractiva estrategia terapéutica.(AU)

Introduction: Rafts are function-structural cell membrane nano-domains. They contribute to explain the efficiency of signal transduction at the low physiological membrane concentrations of the signaling partners by their clustering inside specialized signaling domains. Development: In this article, we review the current model of the membrane rafts and their physio-pathological relevance in the nervous system, including their role in Parkinson, Alzheimer, and Huntington diseases. Conclusions: Rafts disruption/dysfunction has been shown to relate diverse neurological diseases. Therefore, it has been suggested that preservation of membrane rafts may represent a strategy to prevent or delay neuronal dysfunctions in several diseases.(AU)

Tubulin-mediated anatomical and functional changes caused by Ca2+ in human erythrocytes

In previous research, we observed that tubulin can be found in three fractions within erythrocytes, i.e., attached to the membrane, as a soluble fraction, or as part of a structure that can be sedimented by centrifugation. Given that its differential distribution within these fractions may alter several hemorheological properties, such as erythrocyte deformability, the present work studied how this distribution is in turn affected by Ca2+, another key player in the regulation of erythrocyte cytoskeleton stability. The effect of Ca2+ on some hemorheological parameters was also assessed. The results showed that when Ca2+ concentrations increased in the cell, whether by the addition of ionophore A23187, by specific plasma membrane Ca2 + _ATPase (PMCA) inhibition, or due to arterial hypertension, tubulin translocate to the membrane, erythrocyte deformability decreased, and phosphatidylserine exposure increased. Moreover, increased Ca2+ was associated with an inverse correlation in the distribution of tubulin and spectrin, another important cytoskeleton protein. Based on these findings, we propose the existence of a mechanism of action through which higher Ca2+ concentrations in erythrocytes trigger the migration of tubulin to the membrane, a phenomenon that results in alterations of rheological and molecular aspects of the membrane itself, as well as of the integrity of the cytoskeleton. (AU)

Membrana de plasma rica en factores de crecimiento como tratamiento de agujero macular en una paciente vitrectomizada por desprendimiento de retina regmatógeno / Plasma rich in growth factors membrane as a macular hole treatment in a vitrectomized patient due to rhegmatogenous retinal detachment

La formación de un agujero macular tras una vitrectomía por desprendimiento de retina regmatógeno es una complicación rara. Aunque existen diferentes opciones quirúrgicas en el tratamiento de estos agujeros maculares con buenos resultados, se ha demostrado que el antecedente de un desprendimiento de retina con compromiso macular es el factor de riesgo más importante relacionado con la necesidad de múltiples intervenciones para el cierre de estos agujeros, por lo que debe prestarse especial atención al manejo de estos pacientes. Presentamos el caso de una paciente con desprendimiento de retina regmatógeno con compromiso macular que requirió tratamiento con cirugía de catarata, implante de lente intraocular y vitrectomía vía pars plana. Cuatro años después de la cirugía primaria presentó un agujero macular grande y fue tratada con membrana de plasma rica en factores de crecimiento con cierre del agujero macular y mejoría visual sin recidiva 12 meses después de la cirugía (AU)

The formation of a macular hole after vitrectomy due to rhegmatogenous retinal detachment is a rare complication. Although there are different surgical options in the treatment of these macular holes with favorable outcomes, it has been shown that the history of macula-off retinal detachment is the most important risk factor related to the need for multiple interventions to close these macular holes, therefore special attention should be paid in the management of these patients. We present the case of a patient with macula-off rhegmatogenous retinal detachment who required treatment with cataract surgery with intraocular lens implant and pars plana vitrectomy. Four years after the primary surgery, she presented a large macular hole, and was treated with membrane of plasm rich in growth factors with closure of the macular hole and visual improvement without recurrence 12 months after surgery (AU)

Changes in aquaporins expression due to acute water restriction in naturally aging mice

Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration. (AU)

Blockade of exosome release alters HER2 trafficking to the plasma membrane and gives a boost to Trastuzumab

Objective(s) Exosomal HER2 has been evidenced to interfere with antibody-induced anti-tumor effects. However, whether the blockade of HER2+ exosomes release would affect antibody-mediated tumor inhibition has yet to be investigated. Methods Exosomes derived from BT-474, SK-BR3 and SK-OV3 (HER2-overexpressing tumor cells) and MDA-MB-231 cells (HER2 negative) were purified and characterized by bicinchoninic acid (BCA) assay, western blotting and Transmission electron microscopy (TEM). Inhibition of exosome release was achieved by neutral sphingomyelinase-2 (nSMase-2) inhibitor, GW4869. The effects of exosome blockade on the anti-proliferative effects, apoptosis induction, and antibody-mediated cellular cytotoxicity (ADCC) activity of Trastuzumab were examined using MTT, flow cytometry, and LDH release assays. Also, the effects of exosome inhibition on the surface expression and endocytosis/internalization of HER2 were studied by flow cytometry. Results Purified exosomes derived from HER2 overexpressing cancer cells were positive for HER2 protein. Blockade of exosome release was able to significantly improve apoptosis induction, anti-proliferative and ADCC responses of Trastuzumab dose dependently. The pretreatment of Trastuzumab/purified NK cells, but not PBMCs, with HER2+ exosomes could also decrease the ADCC effects of Trastuzumab. Exosome inhibition also remarkably downregulated surface HER2 levels in a time-dependent manner, but does not affect its endocytosis/internalization. Conclusion Based on our findings, HER2+ exosomes may benefit tumor progression by dually suppressing Trastuzumab-induced tumor growth inhibition and cytotoxicity of NK cells. It seems that concomitant blocking of exosome release might be an effective approach for improving the therapeutic effects of Trastuzumab, and potentially other HER2-directed mAbs (AU)

Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer

Iodine is an essential constituent of thyroid hormone. Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC (AU)

Detergentes: De los principios físicos a las aplicaciones biofarmacéuticas (o por qué prevenimos la covid-19 con agua y jabón / Detergents: From physical principles to biopharmaceutical applications (or why we fight covid-19 with toilet soap)

Los detergentes son anfifilos solubles que poseen la capacidad de solubilizar grasas, dando lugar a micelas mixtas lípido-detergente, que son solubles en agua. Los detergentes son ampliamente utilizados en las industrias alimentaria y de bebidas, textil, médica y farmacéutica, entre otras. En biología molecular, los detergentes son herramientas insustituibles en la solubilización de las membranas celulares y la posterior purificación de proteínas de membrana. La presente revisión resume cuatro décadas de investigación sobre detergentes en el laboratorio de los autores. Una introducción sobre los detergentes y las membranas va seguida por una descripción cuantitativa detallada del mecanismo de solubilización de la membrana por los detergentes, y por una discusión crítica del concepto de membranas resistentes a los detergentes en relación con la hipótesis de las balsas lipídicas (rafts). A continuación, se incluye una sección experimental que resume los principales resultados del grupo de los autores. Finalmente, se describen algunas aplicaciones biofarmacéuticas. Como ejemplo práctico, se discute el uso de jabón de tocador en la prevención de la COVID-19

Detergents are soluble amphiphiles that possess the capacity to solubilize fats, giving rise to water-soluble, lipid-detergent mixed micelles. Detergents find an extensive use in food and drink, textile, medical and pharmaceutical industries, among others. In molecular biology, detergents are irreplaceable tools in the solubilization of cell membranes and subsequent membrane protein purification. The present review summarizes four decades of investigation on detergents in the authors' laboratory. An introduction on detergents and membranes is followed by a detailed, quantitative description of the mechanism of membrane solubilization by detergents, and a critical discussion of the concept of detergent-resistant membranes as related to the lipid raft hypothesis. An experimental section follows, summarizing the main results in the authors' group. Finally, some biopharmaceutical applications are described. As a working example, the use of toilet soap in the prevention of COVID-19 is discussed

Dissecting the localization of lipopolysaccharide-responsive and beige-like anchor protein (LRBA) in the endomembrane system

Introduction and objectives: LRBA deficiency is caused by loss of LRBA protein expression, due to either homozygous or compounds heterozygous mutations in LRBA. LRBA deficiency has been shown to affect vesicular trafficking and autophagy. To date, LRBA has been observed in the cytosol, Golgi apparatus and some lysosomes in LPS-stimulated murine macrophages. The objectives of the present study were to study the LRBA localization in organelles involved in vesicular traffic, phagocytosis, and autophagy in mononuclear phagocytes (MP). Materials and methods: We analyzed LRBA colocalization with different endosomes markets using confocal microscopy in MP. We used the autophagy inhibitors to determine the role of LRBA in formation, maturation or degradation of the autophagosome. Results: LRBA intracellular trafficking depends on the activity of the GTPase ADP ribosylation factor-1 (ARF) in MP. LRBA was identified in early, late endosomes but did not colocalize strongly with lysosomal markers. Although LRBA appears not to be recruited during the phagocytic cargo uptake, it greatly colocalized with the microtubule-associated protein 1A/1B-light chain 3 (LC3) under a steady state and this decreased after the induction of autophagy flux. Although the use of inhibitors of lysosome fusion did not restore the LRBA/LC3 colocalization, inhibitors of either early to late endosomes trafficking or PI3K pathway did. Conclusions: Taken together, our results show that LRBA is located in endomembrane system vesicles, mainly in the early and late endosomes. Although LRBA appears not to be involved in the phagocytic uptake, it is recruited in the early steps of the autophagy flux

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Hepatic subcellular distribution of squalene changes according to the experimental setting

Squalene is the main unsaponifiable component of virgin olive oil, the main source of dietary fat in Mediterranean diet, traditionally associated with a less frequency of cardiovascular diseases. In this study, two experimental approaches were used. In the first, New Zealand rabbits fed for 4 weeks with a chow diet enriched in 1% sunflower oil for the control group, and in 1% of sunflower oil and 0.5% squalene for the squalene group. In the second, APOE KO mice received either Western diet or Western diet enriched in 0.5% squalene for 11 weeks. In both studies, liver samples were obtained and analyzed for their squalene content by gas chromatography-mass spectrometry. Hepatic distribution of squalene was also characterized in isolated subcellular organelles. Our results show that dietary squalene accumulates in the liver and a differential distribution according to studied model. In this regard, rabbits accumulated in cytoplasm within small size vesicles, whose size was not big enough to be considered lipid droplets, rough endoplasmic reticulum, and nuclear and plasma membranes. On the contrary, mice accumulated in large lipid droplets, and smooth reticulum fractions in addition to nuclear and plasma membranes. These results show that the squalene cellular localization may change according to experimental setting and be a starting point to characterize the mechanisms involved in the protective action of dietary squalene in several pathologies

Mitochondrial ROS and mtDNA fragments inside nuclear DNA as a main effector of ageing: the «cell aging regulation system» / Fragmentos de mitocondria ROS y mtDNA dentro del ADN nuclear como principal efector del envejecimiento: el sistema de regulación celular de envejecimiento

The updated mitochondrial free radical theory of aging (MFRTA) is reviewed as part of the cell aging regulatory system (CARS). Any valid theory of aging should explain why different animal species age at so different rates. Only two known parameters correlate with species longevity in the right sense: the mitochondrial rate of reactive oxygen species production (mitROSp) and the degree of fatty acid unsaturation of tissue membranes calculated as the double bond index (DBI). Both are low in long-lived animals. Dietary restriction (DR), which increases longevity, also decreases mitROSp and % free radical leak (FRL) at complex I and oxidative damage to mtDNA. This can increase longevity by decreasing mtDNA fragments accumulation inside nuclear DNA which revitalizes MFRTA. Lowered mitROSp and FRL at complex I also occurs during protein or methionine restriction, and rapamycin treatment (which also increases longevity). The decrease in mitROSp during DR (dietary restriction) is due to restriction of a single substance, methionine, and occurs at the matrix domain of complex I. This updated MFRTA focuses on low mitROSp and low sensitivity of membranes to oxidation in long-lived animals. The three best known aging effectors of the genetic Aging Program of aerobic tissues are mitROSp, membrane fatty acid unsaturation, and autophagy. This program reacts to cytoplasmic signaling proteins, influenced by nutrients, drugs and hormones, varying the activity of the mitROSp and macroautophagy aging effectors. An analogous program, although with additional gene clusters of aging involved, and different output activity, can determine longevity in different animal species (AU)

Se revisa la teoría del envejecimiento por radicales libres de origen mitocondrial (MFRTA) como parte del Sistema de Regulación Celular del Envejecimiento (CARS). Cualquier teoría del envejecimiento debe explicar porqué las especies animales envejecen a velocidades tan diferentes. Solo dos parámetros conocidos correlacionan con la longevidad de las especies en el sentido correcto: la producción mitocondrial de radicales de oxígeno (mitROSp) y el grado de insaturación de los ácidos grasos de las membranas celulares. Ambos están disminuidos en las especies longevas. La restricción calórica, de proteínas, o de metionina, y la rapamicina, que aumentan la longevidad, también disminuyen la mitROSp y la fuga % de radicales libres en el complejo I y el daño oxidativo al ADNmt. Esto puede aumentar la longevidad disminuyendo la acumulación de fragmentos del ADNmt dentro del ADN nuclear con la edad, lo cual revitaliza la MFRTA. El descenso en mitROSp durante la restricción calórica se debe sólo a la restricción de metionina, y ocurre en el dominio de membrana del complejo I. La mitROSp, el grado de insaturación de los ácidos grasos, y la autofagocitosis son los tres efectores de envejecimiento conocidos dependientes del programa genético pro-envejecimiento (PAP, que es parte del CARS). El PAP responde a proteínas de señalización celular en función de la disponibilidad de nutrientes y hormonas en los medios ambiente e interno. Este programa, aunque con más clusters génicos del envejecimiento implicados, y con diferente intensidad efectora, podría ser responsable de la regulación de la longevidad de las distintas especies animales (AU)

Primary squamous cell carcinoma of the stomach presenting as a huge retroperitoneal tumor: a case report

A man complained of upper abdominal pain and early satiety for one month. An upper gastrointestinal endoscopy showed nothing special. A CT scan of the abdomen was performed, which demonstrated a huge heterogeneous retroperitoneal mass close to the dorsal wall of the stomach and surrounding the abdominal aortic and celiac trunk. The resected specimen suggested that an irregular tumor invaded the dorsal wall of the stomach. Postoperative histological examination confirmed that it was a gastric squamous cell carcinoma (AU)

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Interacción de FABP4 con proteínas de membrana de células endoteliales / Interaction of FABP4 with plasma membrane proteins of endothelial cells

Introducción: Fatty acid-binding protein 4 (FABP4) es una adipocina secretada por el tejido adiposo implicada en la regulación del metabolismo energético y la inflamación. FABP4 circulante se asocia con obesidad, dislipidemia aterogénica y síndrome metabólico. Estudios recientes muestran una asociación entre FABP4 circulante y disfunción endotelial, aunque se desconoce cómo se produce esta. El objetivo de este trabajo es estudiar la interacción entre FABP4 con las proteínas de la membrana citoplasmática en células endoteliales. Metodología: Se incubaron células HUVEC con y sin FABP4 (100 ng/ml) durante 5 min. La inmunolocalización de FABP4 se estudió mediante microscopia confocal. Para estudiar las interacciones de FABP4 con las proteínas de membrana de las células HUVEC se diseñó una estrategia que combina incubaciones con o sin 6XHistidine-tag FABP4 (FABP4-His) (100 ng/ml), cross-linking con formaldehído, extracción de proteínas de membrana y western blot. Resultados: Los resultados muestran que FABP4 colocaliza con CD31, una proteína utilizada como marcador de membrana citoplasmática. Además se observan diferentes patrones de western blot en función de la incubación con o sin FABP4-His. El inmunoblot revela la existencia de 3 complejos proteicos de aproximadamente 108, 77 y 33 kDa formados por FABP4 exógena y su posible receptor/es. Discusión: Los resultados obtenidos apoyan la existencia de un complejo proteico capaz de unir FABP4 a las células endoteliales mediante una unión específica. Además, nos permiten avanzar en el conocimiento de los efectos moleculares de FABP4 y, en caso de confirmarse, podrían utilizarse como diana terapéutica para prevenir enfermedades cardiovasculares

Introduction: Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function. It is still unknown how the interaction between FABP4 and the endothelial cells is produced to prompt these effects on vascular function. The objective of this work is studying the interaction between FABP4 and the plasma membrane proteins of endothelial cells. Methodology: HUVEC cells were incubated with and without FABP4 (100 ng/ml) for 5 minutes. Immunolocalization of FABP4 was studied by confocal microscopy. The results showed that FABP4 colocalizates with CD31, a membrane protein marker. A strategy which combines 6XHistidine-tag FABP4 (FABP4-His), incubations with or without FABP4-His (100 ng/ml), formaldehyde cross-linking, cellular membrane protein extraction and western blot, was designed to study the FABP4 interactions with membrane proteins of HUVECs. Results: The results showed different western blot profiles depending of the incubation with or without FABP4-His. The immunoblot revelead three covalent protein complexes of about 108, 77 and 33 kDa containing FAPB4 and its putative receptor. Discussion: The existence of a specific binding protein complex able to bind FABP4 to endothelial cells is supported by these results. The obtained results will permit us advance in the molecular knowledge of FABP4 effects as well as use this protein and its receptor as therapeutic target to prevent cardiovascular

Relación entre los ácidos grasos en suero y en los fosfolípidos de membrana en niños sanos / Correspondence between the fatty acids in healthy children serum and in membrane phospholipids

Introducción: La dieta es importante para el suministro de ácidos grasos del hombre, en especial los de las familias n-3 y n-6, por su esencialidad y las amplias funciones fisiológicas relacionadas. Es importante tener valores de referencia en las muestras biológicas accesibles, tales como suero y membranas eritrocitarias, con el fin de paliar posibles déficit. El objetivo del presente trabajo consiste en cuantificar los ácidos grasos esenciales (AGE) presentes en dichas muestras, desde la C6 hasta la C26. Material y métodos: Se han efectuado las determinaciones de los ácidos grasos de 30 niños sanos en suero y en sus correspondientes fosfolípidos de membrana de células sanguíneas, mediante su extracción lipídica, metilación, separación y cuantificación en cromatografía de gases con detección de masas. Se han comparado los valores obtenidos en cada suero y su pareja de membranas celulares. Resultados y discusión: Se han obtenido los valores normales en niños sanos. El C16, que supone la cuarta parte de todos los ácidos grasos, está en la misma proporción en ambas muestras; entre el resto, no se encuentra una correspondencia clara entre ambos valores. Entre los n-6, el C18:2n6 está en mayor proporción en suero, frente al C20:4n6 que lo está en los fosfolípidos. De igual forma, entre los n-3, el C20:5n3 está en mayor proporción en suero y el C22:6n3 lo está en fosfolípidos de membrana. Dichos valores son la causa de procesos distintos, aporte nutricional reciente para el suero y con implicaciones a largo plazo y metabólicas los valores en los fosfolípidos de las membranas (AU)

INTRODUCTION: The diet is important in the supply of fatty acids in humans, especially those of the n-3 and n-6 families by its essentiality and related physiological function. It is important to have reference values in accessible biological samples: serum and erythrocyte membranes, in order to alleviate potential shortfalls. The objective is quantifying fatty acids present in these samples from C6 to C26.MATERIAL AND METHODS: the determinations of the fatty acids of 30 healthy children in serum and its corresponding membrane phospholipids from blood cells by lipid extraction, methylation, separation and quantification in gas chromatography with detection of masses have been. It is comparing the values obtained in each serum and its partner of cell membranes. RESULTS AND DISCUSSION: It is have obtained normal values in healthy children. The C16, which represent a quarter of all fatty acids, it is in the same proportion in both samples, in the rest of fatty acids, there is no clear correspondence between both values. In the n-6 family, the C18:2n6 is higher in serum against the C20:4n6 which is in the phospholipids. In the same way between the n-3 family, the C20:5n3 is higher in serum and the C22:6n3 is in membrane phospholipids. These values are cause of different processes, recent nutritional contribution to serum and with long-term implications and metabolic values in the phospholipids of membranes (AU)

Presence of matrix vesicles in the body of odontoblasts and in the inner thirdof dentinal tissue: A scanning electron microscopyc study

Objectives: The aim of this report is to present the results of a scanning electron microscopic study on the presence of matrix vesicles (MVs) found in human dentine. Study Design: Dentin tissue from 20 human bicuspids was analyzed by means of scanning electron microscopy. Results: MVs were found as outgrowths of the cellular membrane of the odontoblastic body, the more proximal portion of the odontoblastic process before entering the dentinal tubule and in the odontoblastic process within the inner third of the dentin. Size of MVs varied depending on location. In the inner third of dentin, they were seen indiverse positions; as membranal outgrowths, deriving from the odontoblastic process, lying free in the intratubular space and attached to the dentinal wall. Sometimes, they were seen organized forming groups of different size sand shapes or as multivesicular chains running from the surface of the odontoblastic process to the tubular wall. MVs were present in places never considered: 1) the body of odontoblasts; 2) the most proximal part of the odontoblastic processes before entering the circumpulpal dentine and also: 3) in the inner third of dentinal tissue. Conclusions: According to our results, MVs not only participate during mantle dentin mineralization during early dentinogenesis, they also contribute during the mineralization process of the inner dentin (AU)

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum

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Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague–Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1 month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis® homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study (AU)

Mecanismos de acción de los antimicrobianos / Antimicrobial mechanisms of action

Hay una amplia diversidad de familias y grupos de antimicrobianos de interés clínico. Los mecanismos por los que los compuestos con actividad antibacteriana inhiben el crecimiento o causan la muerte de las bacterias son muy variados, y dependen de las dianas afectadas. La pared celular (una estructura singular de la inmensa mayoría de las bacterias, ausente en células eucariotas) puede verse afectada en la síntesis (fosfomicina, cicloserina) o el transporte de sus precursores (bacitracina, mureidomicinas), o en su organización estructural (..) (AU)

A large number of families and groups of antimicrobial agents are of clinical interest. The mechanisms by which compounds with antibacterial activity inhibit growth or cause bacterial death are varied and depend on the affected targets. The bacterial cell wall¿a unique structure in most bacteria that is absent in eukaryotic (..) (AU)

Role of G protein-coupled receptor kinase 2 (GRK2) in migration and inflammation

G protein-coupled receptor kinase 2 (GRK2) emerges as a key modulator of G protein-coupled receptors and other plasma membrane receptors triggered by chemotactic messengers. In addition, GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration. Interestingly, the levels of expression and activity of this kinase are altered in several inflammatory disorders, thus suggesting that it may play an important role in the onset or progression of these pathologies. This review summarizes the mechanisms involved in the control of GRK2 expression and function and highlights novel functional interactions of this protein that might help to explain how altered GRK2 levels affects cell migration in different cell types and pathological settings (AU)

La quinasa GRK2 (G protein-coupled receptor kinase 2) se perfila como un modulador clave de receptores acoplados a proteínas G y de otros receptores de membrana plasmática que responden a estímulos migratorios. Además, GRK2 es capaz de interaccionar con diferentes proteínas señalizadoras relacionadas con la migración celular. Por otra parte, puesto que los niveles de expresión y actividad de esta quinasa se encuentran alterados en distintas en enfermedades inflamatorias, se sugiere que GRK2 puede desempeñar un papel importante en el desencadenamiento o la progresión de estos procesos. Esta revisión resume los mecanismos implicados en el control de la expresión y función de GRK2 y resalta nuevas interacciones funcionales de esta proteína que pueden contribuir a explicar cómo las alteraciones en los niveles de GRK2 afectan a la migración de distintos tipos celulares y a diversas situaciones patológicas (AU)

Regulación de la absorción intestinal de colesterol: el papel protagonista de NPC1L1 y sus polimorfismos funcionales / Regulation of intestinal cholesterol absorption: the prominent role of NPC1L1 and its functional polymorphisms

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