6,319 research outputs found
A role for amphiphysin in AP-1/clathrin coat formation
No full textTransport of cargo within the endocytic and secretory pathway is generally mediated by coated vesicles. Clathrin, in combination with different adaptor proteins, is the major coat protein for vesicle formation at the plasma membrane, endosomes, and the trans-Golgi network (TGN). Best characterized is the formation of clathrin coats for endocytosis at the plasma membrane involving the adaptor protein complex AP-2. Clathrin and AP-2 were shown to be at the centre of a complex interactome of proteins accessory to vesicle formation. Considerably less is known about the formation of clathrin coated carriers at the TGN and endosomes, where the adaptor protein complex AP-1 plays a major role.
In vitro studies showed the minimal requirements for association of AP-1 to liposomal membranes to be activated ARF1, phosphoinositides, and either sorting signals or unknown cytosolic factors. We have used a liposome floatation assay to identify cytosolic proteins collaborating with AP-1 at the membrane. Separation of proteins from bovine brain cytosol with several chromatographic methods yielded an active fraction containing amphiphysin 1, amphiphysin 2, and endophilin A1. All three proteins are expressed in brain and known to be involved in AP-2/clathrin coat formation. They consist of an N-terminal N-BAR (Bin, amphiphysin, Rvs) domain for dimerization and membrane binding and a C-terminal SH3 (Src homology 3) domain for interaction with dynamin and synaptojanin. Amphiphysin 1 and 2 in addition contain a middle domain with binding sites for adaptors and clathrin. It was proposed that amphiphysins and endophilin are targeted to membranes with high curvature, such as the neck of a forming vesicle, where they recruit dynamin and synaptojanin in preparation for vesicle fission and uncoating.
In this thesis, I bacterially expressed and purified all three proteins and tested them in the floatation assay for AP-1 membrane binding activity. Only amphiphysin 2 showed activity, both as a homodimer and as a heterodimer with amphiphysin 1. Activity depended on a motif that was shown to bind to AP-1, AP-2, and clathrin in GST pull-down experiments.
Endogenous amphiphysins in primary neurons, as well as transiently expressed in neuronal or fibroblast cell lines, co-localized with AP-1 at the TGN. In addition, when expressed at high levels in neuronal cells, amphiphysins aggregated and interfered dominantly with the TGN localization of AP-1. Both phenomena depended on the presence of the clathrin and adaptor interaction sequence in the amphiphysins. Furthermore, both amphiphysins could be cross-linked to AP-1 in vivo.
Our results indicate that amphiphysin 1 and 2 function not only in clathrin coated vesicle formation for endocytosis at the plasma membrane, but are also part of the machinery forming AP-1/clathrin coats at the TGN and endosomes. This suggests that the machineries for CCV formation with AP-1 and AP-2 at different locations in the cell share more components than previously anticipated
The Treatment of Ties in AP Correlation
No full textThe Kendall tau and AP correlation coefficients are very commonly use to compare two rankings over the same set of items. Even though Kendall tau was originally defined assuming that there are no ties in the rankings, two alternative versions were soon developed to account for ties in two different scenarios: measure the accuracy of an observer with respect to a true and objective ranking, and measure the agreement between two observers in the absence of a true ranking. These two variants prove useful in cases where ties are possible in either ranking, and may indeed result in very different scores. AP correlation was devised to incorporate a top-heaviness component into Kendall tau, penalizing more heavily if differences occur between items at the top of the rankings, making it a very compelling coefficient in Information Retrieval settings. However, the treatment of ties in AP correlation remains an open problem. In this paper we fill this gap, providing closed analytical formulations of AP correlation under the two scenarios of ties contemplated in Kendall tau. In addition,we developed an R package that implements these coefficients.Best Short Paper Accepted author manuscriptMultimedia ComputingWeb Information System
Las tensiones Estados Unidos-China y el T-MEC : implicaciones para la inversión china en la industria automotriz de México
No full textEsta publicación integra la Mesa de trabajo III: La integración productiva América Latina-Asia Pacífico y los efectos del proteccionismo.Bibliografía: p. 117-118.Samuel Ortiz Velásquez.Introducción -- 1. Diagnóstico sucinto de la industria mexicana -- 2. Las tensiones comerciales China-Estados Unidos: efectos en México -- 3. El T.MEC: implicaciones para la industria en América del Norte -- 4. La inversión china en la IAA de México: situación actual y perspectivas -- 5. Conclusiones y recomendaciones de política
Research on certain properties of an adapted nonlinear reconstruction operator on nonuniform grids
No full text[SPA] Esta tesis doctoral se presenta bajo la modalidad de compendio de publicaciones. Los esquemas de subdivisión y multiresolucion se han utilizado en las últimas décadas en muchas aplicaciones que requieren del diseño geométrico. Estas aplicaciones son numerosas en la industria, por ejemplo, para la fabricación de coches y barcos, y también en la industria cinematográfica para generar diferentes formas tanto en 2D como en 3D: Los esquemas de subdivisión se basan en un proceso de refinamiento sucesivo de un conjunto inicial de datos discretos. Se genera un nuevo conjunto de datos más denso de acuerdo con algunas reglas específicas. A su vez, este nuevo conjunto se refinará aún más. En este punto surgen diversas cuestiones matemáticas importantes, y que van desde asegurar la convergencia de los esquemas a estudiar la suavidad de la función límite, la estabilidad de los esquemas de subdivisión, el orden de aproximación y los requisitos necesarios para su aplicabilidad en problemas de la vida real. En particular, es importante el análisis de las capacidades de preservación de los esquemas para algunas propiedades cruciales que podrán estar presentes en el conjunto inicial de datos, tal como la convexidad. Los esquemas de subdivisión generan algoritmos rápidos para la fácil construcción de curvas y superficies [26], [29]. Todas estas cualidades los convierten en una herramienta interesante para diversas aplicaciones industriales. Además, su estrecha relación con esquemas de multirresolución abre la puerta a más aplicaciones en el campo del procesamiento de datos y señales. Los procesos de compresión y eliminación de ruido son fáciles de implementar mediante el uso de esquemas de multiresolución y se ha comprobado que son bastante eficientes. Véase, por ejemplo [35], [5], [2]. Una cuestión principal a la hora de elegir un esquema de subdivisión adecuado es la propiedad de conservación de la convexidad, porque muchas aplicaciones la requieren. Se han hecho muchos esfuerzos en este sentido, véase por ejemplo [27], [32], [33], [37]. La estabilidad es también un problema principal en las aplicaciones de la vida real, ya que los diseños finales se generan mediante el refinamiento de un conjunto inicial de puntos que suele estar afectado por algún error. Por lo tanto, es esencial hacer un seguimiento del error y mantenerlo por debajo de una tolerancia prescrita. Algunas referencias recomendadas sobre la estabilidad de los esquemas de subdivisión y multiresolución pueden consultarse en [24], [9], [11], [1], [3], [15]. Harten derivó una teoría que conecta estrechamente los operadores de reconstrucción con los esquemas de subdivisión y multiresolución [35], [5]. Las reconstrucciones no lineales aparecen como una buena opción para minimizar los efectos adversos de las posibles singularidades y para mejorar la adaptación a los datos dados. Esta teoría no es tan fácil de estudiar como para el caso lineal. Los operadores de reconstrucción no lineales dan lugar a esquemas de subdivisión y multiresolución no lineales. Para dejar claro el tipo de dificultades que se pueden encontrar, mencionamos por ejemplo el caso del análisis de estabilidad. A este respecto, se ha demostrado que todos los esquemas de subdivisión y multiresolución lineales son estables, mientras que se necesita un análisis particular para cada esquema no lineal concreto. Los esquemas de multiresolución están profundamente conectados con los esquemas de subdivisión y heredan muchas de sus propiedades. Para más información sobre estas herramientas se puede consultar [5] como primera referencia. En [6] se introdujo una reconstrucción no lineal denominada PPH y se estudio el esquema de subdivisión asociado. Esta reconstrucción se definió con el fin de adaptarse a la presencia de potenciales singularidades. Consiste en una modificación ingeniosa de la interpolación centrada de cuarto orden de Lagrange a trozos. Para implementar la adaptación, la reconstrucción se realiza localmente en un intervalo [xj ; xj+1] usando los valores disponibles de la función en las cuatro abscisas centradas fxj1; xj ; xj+1; xj+2g; y teniendo en cuenta dos aspectos principales. El primer aspecto es que la modificación en un área donde la función subyacente es suave debe hacerse de tal manera que las cantidades alteradas no cambien significativamente, de modo que la modificación siga siendo O(h4); donde h representa el espaciado del mallado. El segundo aspecto es que, en los intervalos adyacentes a una singularidad, pero que no la contienen, la reconstrucción conserve cierto orden de aproximación, de hecho O(h2); al contrario de lo que ocurre con su homólogo lineal que pierde completamente el orden de aproximación. Esta tesis se dedica principalmente al estudio del operador de reconstrucción no lineal PPH en mallados no uniformes. En algunos casos y para demostrar determinados resultados teóricos haremos uso de mallados σ cuasi uniformes, que no son otra cosa que un tipo de mallados no uniformes que aparecen en casi todas las aplicaciones prácticas. La definición exacta se da más adelante.[ENG] This doctoral dissertation has been presented in the form of thesis by publication. Subdivision and multiresolution schemes have been used in the last few decades in many ap- plications that require from geometrical design. These applications are numerous in industry, for example for car and ship manufacturing, and also in the film industry in order to generate different shapes as much in 2D as in 3D. Subdivision schemes are based on a process of successive refine- ment of a given initial discrete data set. A new denser set of data is generated according to some specific rules. In turn, this new set will be further refined. A bunch of important mathematical questions arise at this point, and range from ensuring the convergence of the schemes, studying the smoothness of the limit function, the stability of the subdivision schemes and the order of approxi- mation and the necessary requirements for their applicability in real life problems. In particular, it is important the analysis of the preservation capabilities of the schemes for some crucial properties which might be present in the initial set of data such as it could be the convexity. Subdivision schemes generate fast algorithms to the easy construction of curves and surfaces [26], [29]. All these qualities make them an interesting tool for several industrial applications. Also, their close relation to multiresolution schemes opens the door to more applications in the fields of data and signal processing. Compression and denoising processes are easy to implement by using multiresolution schemes and they have been tested to be quite efficient. See for example [35], [5], [2]. A chief issue in choosing an adequate subdivision scheme is the property of convexity preser- vation, because many application require it. Many efforts have been done in this sense, see for example [27], [32], [33], [37]. Stability is also a main issue in real life applications, since the final designs are generated through the refinement of an initial set of points which usually is affected by some error. Therefore, keeping track of the error and maintaining it under a prescribed tolerance is essential. Some recommended references about stability of subdivision and multiresolution schemes can be consulted in [24], [9], [11], [1], [3], [15]. Harten derived a theory which closely connects reconstruction operators with subdivision and multiresolution schemes [35], [5]. Nonlinear reconstructions appear as a good option to minimize the adverse effects of potential singularities and to improve the adaptation to the given data. This theory is not as easy to study as for the linear case. Nonlinear reconstruction operators give rise to nonlinear subdivision and multiresolution schemes. In order to let clear the kind of difficulties to be encountered, we mention for example the case of stability analysis. In what stability issues regards, all linear subdivision and multiresolution schemes are proved to be stable, while a particular analysis is needed for each particular nonlinear scheme. Multiresolution schemes are deeply connected with subdivision schemes and they inherit many of their properties. For more information about these useful schemes one can consult [5] as a first reference.
In [6] a nonlinear reconstruction called PPH was introduced, and the associated subdivision scheme was studied. This reconstruction was built in order to get adapted to the presence of potential singularities. It consist on a witty modification of the centered fourth order piecewise Lagrange interpolation. In order to implement the adaptation, the reconstruction is built also locally using a stencil of four centered data, but keeping in mind two main concerns. The first concern is that the modification in an area where the underlying function is smooth must be done in such a way that the modified quantities are not significatively changed, so that the modification remains O(h4), where h stands for the grid size. The second concern is that in the intervals adjacent to a singularity, but not containing it, the reconstruction retains some order of approximation, in fact O(h2), on the contrary to what happens with its linear counterpart that loses completely the approximation order. [ENG] Subdivision and multiresolution schemes have been used in the last few decades in many ap- plications that require from geometrical design. These applications are numerous in industry, for example for car and ship manufacturing, and also in the film industry in order to generate different shapes as much in 2D as in 3D. Subdivision schemes are based on a process of successive refinement of a given initial discrete data set. A new denser set of data is generated according to some specific rules. In turn, this new set will be further refined. A bunch of important mathematical questions arise at this point, and range from ensuring the convergence of the schemes, studying the smoothness of the limit function, the stability of the subdivision schemes and the order of approximation and the necessary requirements for their applicability in real life problems. In particular, it is important the analysis of the preservation capabilities of the schemes for some crucial properties which might be present in the initial set of data such as it could be the convexity. Subdivision schemes generate fast algorithms to the easy construction of curves and surfaces [26], [29]. All these qualities make them an interesting tool for several industrial applications. Also, their close relation to multiresolution schemes opens the door to more applications in the fields of data and signal processing. Compression and denoising processes are easy to implement by using multiresolution schemes and they have been tested to be quite efficient. See for example [35], [5], [2]. A chief issue in choosing an adequate subdivision scheme is the property of convexity preservation, because many application require it. Many efforts have been done in this sense, see for example [27], [32], [33], [37]. Stability is also a main issue in real life applications, since the final designs are generated through the refinement of an initial set of points which usually is affected by some error. Therefore, keeping track of the error and maintaining it under a prescribed tolerance is essential. Some recommended references about stability of subdivision and multiresolution schemes can be consulted in [24], [9], [11], [1], [3], [15]. Harten derived a theory which closely connects reconstruction operators with subdivision and multiresolution schemes [35], [5]. Nonlinear reconstructions appear as a good option to minimize the adverse effects of potential singularities and to improve the adaptation to the given data. This theory is not as easy to study as for the linear case. Nonlinear reconstruction operators give rise to nonlinear subdivision and multiresolution schemes. In order to let clear the kind of difficulties to be encountered, we mention for example the case of stability analysis. In what stability issues regards, all linear subdivision and multiresolution schemes are proved to be stable, while a particular analysis is needed for each particular nonlinear scheme. Multiresolution schemes are deeply connected with subdivision schemes and they inherit many of their properties. For more information about these useful schemes one can consult [5] as a first reference. In [6] a nonlinear reconstruction called PPH was introduced, and the associated subdivision scheme was studied. This reconstruction was built in order to get adapted to the presence of potential singularities. It consists on a witty modification of the centered fourth order piecewise Lagrange interpolation. In order to implement the adaptation, the reconstruction is built also locally using a stencil of four centered data but keeping in mind two main concerns. The first concern is that the modification in an area where the underlying function is smooth must be done in such a way that the modified quantities are not significatively changed, so that the modification remains O(h4), where h stands for the grid size. The second concern is that in the intervals adjacent to a singularity, but not containing it, the reconstruction retains some order of approximation, in fact O(h2), on the contrary to what happens with its linear counterpart that loses completely the approximation order.Escuela Internacional de Doctorado de la Universidad Politécnica de CartagenaPrograma de Doctorado en Tecnologías IndustrialesEsta tesis doctoral se presenta bajo la modalidad de compendio de publicaciones. Está formada por estos siete artículos:
1.Jiménez, I.; Ortiz, P.; Ruiz, J.; Trillo, J. C.; Yañez, D. F. Improving the stability bound for the PPH nonlinear subdivision scheme for data coming from strictly convex functions. Applied Mathematics and Computations. 2021, https://doi.org/10.1016/j.amc.2021.126042. 2. Ortiz, P.; Trillo, J.C. On the Convexity Preservation of a Quasi C3 Nonlinear Interpolatory Reconstruction Operator on σ Quasi-Uniform Grids. Mathematics. 2021, 9(4), 310. https://doi.org/10.3390/math9040310. 3. Ortiz, P.; Trillo, J.C. A Piecewise Polynomial Harmonic Nonlinear Interpolatory Reconstruction Operator on Non Uniform Grids{Adaptation around Jump Discontinuities and Elimination of Gibbs Phenomenon. Mathematics. 2021, 9, 335. https://doi.org/10.3390/math9040335. 4. Amat, S.; Ortiz, P.; Ruiz, J.; Trillo, J. C.; Yanez, D. F. Improving the approximation order around inection points of the PPH nonlinear interpolatory reconstruction operator on nonuniform grids. 5. Ortiz, P.; Trillo, J.C. On certain inequalities associated to curvature properties of the nonlinear PPH reconstruction operator. Journal of Inequalities and Applications. 2019, Paper No. 8, 13 pp, https://doi.org/10.1186/s13660-019-1959-0. 6. Ortiz, P.; Trillo, J.C. Analysis of a New Nonlinear Interpolatory subdivision scheme on σ quasi-uniform grids. Mathematics. 2021, 9, 1320. https://doi.org/10.3390/math9121320. 7. Amat, S. ; Ortiz, P.; Ruiz, J.; Trillo, J.C. ; Yáñez, D.F. Graphical interpretation of the weighted harmonic mean of n positive values and applications.Universidad Politécnica de Cartagen
La armonía del devenir: zen y poesía en Juan L. Ortiz
No full textEn este ensayo exploro la relación que existe en la poesía del poeta argentino Juan L. Ortiz, entre la experiencia poética y la iluminación o satori de la filosofía zen. Juan L. Ortiz, por medio de la contemplación de su paisaje natal-cotidiano, logra acceder a un nivel de conciencia en el que entrevé la maravilla de la compenetración del uno con el todo. La renuncia a sí mismo, la atención hacia las cosas por más ínfimas que éstas sean, la aceptación del vacío como fundamento de la existencia, lo llevan a ver al amor como la única respuesta para recobrar su propia armonía.La poesía para Ortiz supone entonces la posibilidad de acceder, mediante el leguaje, a esa armonía tan deseada. Un eje importante de este ensayo es el de mostrar cómo el lenguaje de Ortiz logra configurar en su interior esa experiencia, cómo construye un lenguaje que él mismo calificó de “transparente”, y cómo ese lenguaje logra contener en sí la armonía del devenir.I am exploring in this essay the relation in Argentinian poet Juan L. Ortiz’s poetry, between the poetic experience and the zen philosophy of enlightenment or satori. Through the contemplation of the landscape in his everyday fatherland, Juan L. Ortiz reaches consciousness in which he perceives the wonder of one being one with everything. Renouncement of one’s self, attention to the smallest of things, acceptance of the void as basis of our existence, take him to see love as the only answer to recover harmony.Ortiz’s poetry gives then the possibility to enter, through language, to that harmony he so aspires. An important axis in this essay is to present how Ortiz’s language succeeds to configure within itself that experience, how he builds up a language which he himself denominated “transparent”, and how this language contains within itself the harmony of becoming
Delamination Analysis of A Class of AP-PLY Composite Laminates
No full textA recently developed fiber placement architecture, AP-PLY, has been shown to give significantly improved damage tolerance characteristics of composite structures. The behavior of delaminations resulting from low speed impact damage is of particular concern. Major attention has been paid to expand current knowledge on the delamination response of simple AP-PLY composite structure and move towards in-depth understanding of the failure mechanisms behind the damage tolerance. This thesis presents the approaches to predict delamination onset and analyze delamination growth, in support of the search of the optimum woven pattern for AP-PLY composite laminates. The recovered interlaminar stress between layers combined with the maximum stress criterion determined the delamination onset of simple AP-PLY composite laminate under out-of-plane loads. 2D finite element models with cohesive elements inserted in the interfaces of woven layers have been built to evaluate the delamination initiation and propagation in the different woven patterns of simple AP-PLY composite beams. The parameters of the woven pattern, such as the woven angle, the number of woven plies, the number of straight filled plies, and the location of the woven patterns in through the thickness direction, were investigated and shown to have a significant effect on delamination creation and growth. An energy method based on beam theory was proposed to analyze the strain energy release rate (SERR) of an existing crack in an AP-PLY beam structure. The developed analytical method was implemented in isotropic materials and the obtained SERR of a crack was validated by reference results and finite element solutions. The general behavior of crack growth on the left or right crack tip was evaluated and basic trends leading to crack propagation on one side of the crack were established. A correction factor was introduced to improve the accuracy of the SERR of a small crack through the numerical calculation. The singularity of crack tip caused by dissimilar materials was investigated and was found that the inclusion of the singularity effect could increase the accuracy for small cracks. It has been shown that the neutral axis needs to be relocated to decouple the bending and membrane behavior of unsymmetrical composite laminates, thus to meet the requirement of minimizing the strain energy of the delaminated beam to calculate the SERR of a delaminated composite beam. The calculated SERR of a crack in a composite beam has been verified by comparing with a finite element model. The woven plies in AP-PLY composite laminate altered the layup and two conventional laminates with different stacking sequences were identified in an AP-PLY composite laminate based on the assumption that the resin areas were ignored. A step by step approach was developed to obtain the SERR of a crack that goes across different materials. The analytical SERR determined when two materials are used in sequence, sets the stage for optimization of AP-PLY composite laminates without taking account of the effect of the resin area. The procedure of optimization of simple AP-PLY pattern was proposed and industry may benefit for many applications. An equivalent stiffness approach was used to model regions containing resin pockets and straight or inclined composite layers. A series of three point bending tests was carried out where the failure process and loading capacity were evaluated. The methodology, procedure of optimization, philosophy outlined in this thesis might also be applied to the more complicated fully woven AP-PLY composite laminates. The work in this thesis contributes to the understanding of the behavior of AP-PLY composite laminates with delaminations
Structure function analysis of blazars AP Librae and 3c279
No full textHighest Honors in AstronomyBlazars AP Librae and 3c279 are analyzed for microvariability using a technique known as structure function analysis. AP Librae was observed in April
of 2005 and 3c279 was observed in April of 2007. The data for AP Librae was
previously reduced by Andrew Collazzi and the author reduced the data for
3c279. Both sets of data were reduced using Robert Knop's data reduction
program.
The author ran structure function analysis on both sets of data. Structure function analysis is a statistical analysis run on data that is suppose to
nd timescales of variability, periodicity, and the noise type of data. Previous analysis of AP Librae confirmed mircrovariability, which also shows up in
the structure function of AP Librae. Blazar 3c279 was much quieter than AP
Librae and showed no microvariability durning any of the nights.College of Arts and ScienceDepartment of Physics and Astronom
AP-based wireless intrusion detection systems
No full textThis thesis was scanned from the print manuscript for digital preservation and is copyright the author.
Researchers can access this thesis by asking their local university, institution or public library to
make a request on their behalf. Monash staff and postgraduate students can use the link in the References field
Actividad antimicrobiana de DCF-AP enaminona sobre enterococcus faecalis: estudio in vitro.
No full textObjetivo: Evaluar el efecto antibacteriano in vitre de Enaminona (DFC-AP) contra E.
faecalis.
Materiales y métodos: Se utilizó 1µl de la cepa de Enterecoccus faecalis con un recuento microbiano de 6 X 105 ufc/ml en soluciones de 2001-11 para la prueba cualitativa y para la prueba cuantitativa se utilizó 100µl de cada grupo experimental y 100µl del medio de cultivo con E. faecalis. Las muestras se dividieron en 3 grupos: grupo 1- Agua desionizada estéril (control positivo), Grupo 2- Hipoclorito de Sodio al 5.25 y 1% como estándar de oro (control negativo), Grupo 3- Enaminona EFC-AP a concentraciones 500, 250,62,30 y 151µg/µl (material de estudio). A las 24 hrs se observó de manera cualitativa el crecimiento bacteriano en placas de agar de caldo cerebro corazón (BHI) y cuantitativamente en microplacas de 96 pozos en repeticiones de 10 X en donde la concentración de UFC se estimó a base de la absorbancia del crecimiento bacteriano de las muestras mediante espectrofotometría.
Resultados: De manera visual y cualitativamente se comprobó la eficacia antimicrobiana del compuesto Enaminona EFC-AP en donde se identificó un crecimiento de células inversamente proporcional a las concentraciones utilizadas y de manera cuantitativa se obtuvo un crecimiento bacteriano de 1.0 X 105 - 2.6 X 105 ufc/ml en las concentraciones 500, 250 y 125 µg/µl resultando ser las de mayor eficacia antimicrobiana, así mismo el estándar de oro obtuvo un crecimiento bacteriano de 5.0 X 104 ufc/ml y en su comparación no se encontró diferencia estadísticamente significativa con un valor de p>0.05, y aunado a esto registró una correlación negativa moderada entre la concentración del grupo de estudio y las UFC.
Conclusiones: Se comprobó cuantitativa y cualitativamente que el compuesto Enaminona EFC-AP tiene eficacia antibacteriana in vitre contra E. faecalis, obteniendo
resultados similares con el estándar de oro en las concentraciones 500,250 y 125 µg/µl y siendo esta última concentración la mínima dosis inhibitoria.InvestigadoresEstudiante
Environmental toxicity, redox signaling and lung inflammation:the role of glutathione
No full textGlutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox-sensitive transcription factors such as Nrf2, NF-kappaB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation of GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-l-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease
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