Factor 1 inducible por hipoxia y enfermedad pulmonar obstructiva crónica: respuestas epigenéticas al ejercicio físico. Revisión sistemática / Hypoxia-inducible factor 1 and chronic obstructive pulmonary disease: Epigenetic responses to physical exercise. Systematic review

Antecedentes: El ejercicio físico es una de las principales recomendaciones para la mejora de la calidad de vida de las personas con enfermedad pulmonar obstructiva crónica (EPOC). El ejercicio genera múltiples reacciones moleculares que favorecen el ciclo y funcionamiento celular a partir de estímulos que modulan la transcripción y traducción de genes mediados por el factor 1 inducible por hipoxia (HIF-1). Objetivo: Determinar el conocimiento actual sobre las respuestas epigenéticas mediadas por HIF-1 y su comportamiento posterior a la práctica del ejercicio físico en personas con EPOC. Métodos: Búsqueda de artículos en las bases de datos Science Direct, PubMed, Scielo y PEDro. Se emplearon los términos de búsqueda Chronic obstructive pulmonary disease; Hypoxia; Hypoxia-inducible factor 1; Epigenomics; Exercise. Criterios de inclusión: publicaciones que presentaran las respuestas biomoleculares reguladas por HIF-1 en personas con EPOC. Criterios de exclusión: publicaciones de personas con diagnóstico de anemia, enfermedad hepática, enfermedad renal o antecedentes de hemorragia digestiva. Resultados: Se identificaron 75 estudios, de los cuales se seleccionaron 40 con posterioridad al cumplimiento de criterios de inclusión y exclusión. Se encontraron diferencias sobre las modificaciones postranscripcionales para la expresión de genes que favorecen al transporte hematológico de O2, el incremento del metabolismo oxidativo y el favorecimiento de la angiogénesis en el tejido muscular en personas con EPOC posterior a la práctica de ejercicio físico. Conclusiones: Las investigaciones en torno a las respuestas del HIF-1 en personas con EPOC son contradictorias. Se encuentran estudios que estipulan una retroalimentación positiva del HIF-1 para la expresión o silenciamiento de genes susceptibles al O2 y otros que plantean retroalimentación negativa. Es necesario realizar más estudios sobre las respuestas mediadas por HIF-1 en personas con EPOC y que realizan ejercicio físico.

Background: Physical exercise is one of the main recommendations for improving the quality of life of people with chronic obstructive pulmonary disease (COPD). Exercise generates multiple molecular reactions that promote cell cycle and function from stimuli that modulate the transcription and translation of genes mediated by hypoxia-inducible factor 1 (HIF-1). Objective: To determine the current knowledge about the epigenetic responses mediated by HIF-1 and their behavior after the practice of physical exercise in people with COPD. Methods: Search for articles in the Science Direct, PubMed, Scielo and PEDro databases. Se search terms Chronic Obstructive Pulmonary Disease; Hypoxia; Hypoxia-Inducible Factor 1; Epigenomics; Exercise. Inclusion criteria: publications presenting the biomolecular responses regulated by HIF-1 in people with COPD. Exclusion criteria: publications of people with a diagnosis of anemia, liver disease, kidney disease or a history of gastrointestinal bleeding. Results: Seventy-five studies were identified, of which 40 were selected after meeting the inclusion and exclusion criteria. Differences were found on the post-transcriptional modifications for the expression of genes that favor the hematological transport of O2, the increase in oxidative metabolism and the favoring of angiogenesis in muscle tissue in people with COPD after practicing physical exercise. Conclusions: Research on HIF-1 responses in people with COPD is conflicting. There are studies that stipulate a positive feedback of HIF-1 for the expression or silencing of genes susceptible to O2 and others that pose negative feedback. More studies are needed on HIF-1-mediated responses in people with COPD and those who engage in physical exercise.

Revisión sistemática de los indicadores utilizados en el diagnóstico del síndrome de sobreentrenamiento en atletas / Systematic review of the indicators used in the diagnosis of Overtraining Syndrome in athletes

Introducción El éxito de un proceso de entrenamiento deportivo radica en la adaptación satisfactoria del atleta al aumento progresivo de la carga, que incluye respetar los tiempos de recuperación. Sin embargo, cuando esto no ocurre puede aparecer el Síndrome de Sobreentrenamiento (SSE). Objetivo Establecer a través de la revisión de evidencia sistemática, los indicadores utilizados para el diagnóstico del SSE en atletas de resistencia de alto rendimiento. Método Se realizó una búsqueda sistemática de los indicadores utilizados en el diagnóstico del SSE en las bases de datos PubMed, Embase, Cochrane, Science Direct, Biomed Central y Scielo. Se evaluó calidad, sesgo y heterogeneidad de cada publicación, para un posterior análisis cualitativo o cuantitativo de acuerdo con la información encontrada para cada variable. Resultados Once artículos (con 7 estudios) fueron seleccionados para análisis completo. Cinco variables (lactato, creatin quinasa, cortisol, VO2 máx y FC máx) fueron incluidas para análisis cuantitativo. Tres de las variables presentaron heterogeneidad baja y dos heterogeneidad moderada. El lactato demostró una disminución consistente en el grupo experimental (DM -1,86 IC 95% -2,66 a -1,07). La FC máx también se vio disminuida en el grupo experimental (DM -4,08 IC 95% -8,41 a 0,24). Conclusiones Se encontró que la monitorización del lactato y de la FC máxima podrían ser indicadores cercanos al diagnóstico del SSE (AU)

Introduction The success of a sports training process lies in the satisfactory adaptation of the athlete to the progressive increase of load, respecting recovery times. However, when this does not occur, overtraining syndrome (OTS) may appear. Objective To establish through the review of systematic evidence, the indicators used for the diagnosis of OTS in high performance endurance athletes. Method A systematic search was carried out in the PubMed, Embase, Cochrane, Science Direct, Biomed Central and Scielo databases. Quality, bias, and heterogeneity of each publication were evaluated, for a subsequent qualitative or quantitative analysis according to the information found for each variable. Results Eleven articles (with 7 studies) were selected for complete analysis. 5 variables (lactate, creatin kinase, cortisol, VO2 max and HR max) were included for quantitative analysis. Three of the variables presented low heterogeneity and 2 moderate heterogeneity. Lactate showed a consistent decrease in the experimental group (SD -1.86 95% CI -2.66 to -1.07). HR max also decreased in the experimental group (DM -4.08 95% CI -8.41 to 0.24). Conclusions It was found that lactate and maximal HR monitoring could be indicators close to diagnosis of OTS (AU)

Male genital and wing morphology in the cactophilic sibling species Drosophila gouveai and Drosophila antonietae and their hybrids reared in different host plants.

Cactophilic Drosophila flies are excellent models to study adaptation to a relatively narrow spectrum of potential host plants and host-driven evolutionary diversification. Previous studies suggested a complex genetic architecture of wing and male genital morphology in phylogenetically basal species of the D. buzzatii cluster. In this work, we investigate the effect of experimental hybridization and host plant shifts on male genital and wing morphology in D. gouveai Tidon-Sklorz and Sene and D. antonietae Tidon-Sklorz and Sene, a pair of more recently derived species. We explicitly tested the hypotheses that wing and male genital morphology in interspecific hybrids depend on the host plant in which flies were grown. Our study shows that cactus hosts exert a strong effect on genital and wing morphology and that hybrids can be clearly differentiated on the basis of wing and genital morphology from both parental species. However, the extent of morphological differentiation between hybrids and pure species as well as plasticity patterns varied across organs, suggesting a complex genetic architecture for the studied traits.

Wing morphology and fluctuating asymmetry depend on the host plant in cactophilic Drosophila.

As in most insect groups, host plant shifts in cactophilic Drosophila represent environmental challenges as flies must adjust their developmental programme to the presence of different chemical compounds and/or to a microflora that may differ in the diversity and abundance of yeasts and bacteria. In this context, wing morphology provides an excellent opportunity to investigate the factors that may induce changes during development. In this work, we investigated phenotypic plasticity and developmental instability of wing morphology in flies on the cactophilic Drosophila buzzatii and Drosophila koepferae raised on alternative breeding substrates. We detected significant differences in wing size between and within species, and between flies reared on different cactus hosts. However, differences in wing shape between flies emerged from different cactus hosts were not significant either in D. buzzatii or in D. koepferae. Our results also showed that morphological responses involved the entire organ, as variation in size and shape correlated between different portions of the wing. Finally, we studied the effect of the rearing cactus host on developmental instability as measured by the degree of fluctuating asymmetry (FA). Levels of FA in wing size were significantly greater in flies of both species reared in non-preferred when compared with those reared in preferred host cacti. Our results are discussed in the framework of an integrative view aimed at investigating the relevance of host plant shifts in the evolution of the guild of cactophilic Drosophila species that diversified in South America.

Purification of a heterodimeric betaine aldehyde dehydrogenase from wild amaranth plants subjected to water deficit.

Betaine aldehyde dehydrogenase was purified to homogeneity from wild-type amaranth plants subjected to water deficit. The enzyme has a native molecular mass of 125 kDa; it is formed by two subunits, one of the subunits with a molecular mass of 63 kDa and the second one of 70 kDa as determined by SDS-PAGE and double dimension electrophoresis. IEF studies showed two bands with pI values of 4.93 and 4.85, respectively. Possible glycosilation of the 63- and 70-kDa subunits were tested with negative results. Both subunits cross-reacted strongly with polyclonal antibody raised against porcine kidney BADH. Also antiserum rose against HSP70 cross-reacted strongly with the wild amaranth BADH 70-kDa subunit. The enzyme was stable to extreme pH's and temperatures, and high KCl concentrations. Product inhibition of BADH was not observed.

Struma ovarii: tres presentaciones clínicas diferentes en un infrecuente tumor de ovario / Struma ovarii: three presentations of an uncommon ovarian tumor

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Kinetic study of porcine kidney betaine aldehyde dehydrogenase.

Porcine kidney betaine aldehyde dehydrogenase (EC 1.2.1.8) kinetic properties were determined at low substrate concentrations. The double-reciprocal plots of initial velocity versus substrate concentration are linear and intersect at the left of the 1/v axis and showed substrate inhibition with betaine aldehyde. Studies of inhibition by NADH and dead-end analogs showed that NADH is a mixed inhibitor against NAD(+) and betaine aldehyde. AMP is competitive with respect to NAD(+) and mixed with betaine aldehyde. Choline is competitive against betaine aldehyde and uncompetitive with respect to NAD(+). The kinetic behavior is consistent with an Iso-Ordered Bi-Bi Steady-State mechanism.

Immunolocalization of betaine aldehyde dehydrogenase in porcine kidney.

Polyclonal anti-BADH serum was raised in rabbits against native BADH purified from porcine kidney. The antiserum cross-reacted strongly with BADH purified from kidney, Amaranthus palmierii, and Pseudomona aeuroginosa (1:1000), and weakly with Amaranthus hypochondriacus L (1:100). Antibodies bound to purified native kidney BADH in immunoblots showed a major band of an apparent molecular mass of 340 kDa and a subunit with an apparent molecular mass of 52 kDa. Data on activity assays showed higher activity in cortex sections (81.3 nmol/min/mg protein) than in medulla sections (21.3 nmol/min/mg protein). Immunolocalization of BADH in kidney tissue sections showed that BADH is found in cortex and medulla. In inner medulla, the enzyme was mainly localized in cells surrounding the tubules. Western blot analysis on extracts from the cortex and medulla sections showed higher concentration of BADH protein in cortex than in medulla. These results were in accordance with immunolocalization and activity analysis.

Porcine kidney betaine aldehyde dehydrogenase: purification and properties.

Significant betaine aldehyde dehydrogenase activity was found in porcine kidney. The enzyme was purified 320-fold with an overall recovery of 11%. It had a specific activity of 115.8 nkats/mg protein and proved to be homogeneous by SDS-PAGE with a subunit molecular mass of 52 kDa. IEF studies showed three bands with pI values of 5.74, 5.68 and 5.58, respectively. The enzyme was stable in a pH range between 5.0 and 10.0 and the optimum pH was 9.5. The reaction is highly specific for NAD+ and betaine aldehyde, although acetaldehyde, butyraldehyde and glyceraldehyde can be used. Estimated values of Km at pH 8.0 and 25 degrees C were 127 microM for betaine aldehyde and 40 microM for NAD+. The reaction could not be reversed even at high glycine betaine concentrations. The enzyme was not activated by salts at high concentrations but it was salt tolerant-retaining 50% of maximal activity at 1.0 M K+ and Na+. It is inferred that salt tolerance is an essential property for an enzyme participating in the cellular synthesis of an osmoprotectant. Proline, glycerol, sucrose and mannitol had a little effect on the enzyme activity while glycine betaine had an inhibitory effect.

Substrate inhibition by betaine aldehyde of betaine aldehyde dehydrogenase from leaves of Amaranthus hypochondriacus L.

We have previously proposed that at low substrate concentrations betaine aldehyde dehydrogenase follows an irreversible Iso Ordered Bi Bi Steady State kinetic mechanism with NAD+ as the leading substrate [E.M. Valenzuela-Soto and R.A. Muñoz-Clares, J. Biol. Chem. 268 (1993) 23818-23823]. To further the understanding of this enzyme, we have studied the kinetics at high substrate concentrations. Betaine aldehyde at concentrations above 500 microM behaves as a non-competitive inhibitor against NAD+, with downward-curved slope and intercept replots. Double-inhibition studies, using NADH as the second inhibitor, show the formation of the abortive ternary complex enzyme NADH betaine aldehyde, from which NADH may escape at a finite rate, accounting for the nonlinear Dixon plots obtained for both inhibitors. In addition, the binary complex enzyme x betaine aldehyde may give rise to a slower alternative route of reaction, which, under our experimental conditions, was observed at NAD+ concentrations above 1 mM, where double-reciprocal plots of initial velocity against [NAD+] and Dixon plots of 1/v against [NADH] were concave downward. In contrast with other aldehyde dehydrogenases, no 'substrate activation' by the aldehyde was observed under several conditions, which is consistent with the alternative route of reaction being slower than the route which operates at low substrate concentrations. Taken together, our results are consistent with the partial inhibition by high betaine aldehyde concentrations resulting from an irreversible Iso Random Steady State mechanism with a preferential route of reaction. Eventually, at very high betaine aldehyde concentrations, the kinetic mechanism may change to an apparent Ping Pong.

Betaine-aldehyde dehydrogenase from leaves of Amaranthus hypochondriacus L. exhibits an Iso Ordered Bi Bi steady state mechanism.

The kinetics of the oxidation of betaine aldehyde catalyzed by NAD(+)-betaine-aldehyde dehydrogenase, purified from amaranth leaves subjected to water deficit, were analyzed by steady state initial velocity and product and dead-end inhibition studies at low substrate concentrations. Only one product, NADH, gives inhibition. The other product of the reaction, glycine betaine, does not inhibit the enzyme even at concentrations as high as 10 mM. In dead-end inhibition experiments, AMP and choline were used as dead-end analogs of NAD+ and betaine aldehyde, respectively. The families of double-reciprocal plots in the range 0.010-0.500 mM NAD+ and 0.025-0.300 mM betaine aldehyde are linear and intersect at the left of the 1/v axis. NADH is a mixed inhibitor against NAD+ and betaine aldehyde. AMP is competitive with respect to NAD+ and mixed with betaine aldehyde. Choline is competitive against betaine aldehyde and uncompetitive with respect to NAD+. Our results are consistent with an Iso Ordered Bi Bi steady state mechanism in which NAD+ is the first substrate to bind to the enzyme and NADH is the last product to dissociate from it. To our knowledge, this is the first time that an Iso mechanism has been demonstrated by product inhibition studies, as predicted by Cleland (Cleland, W. W. (1963) Biochim. Biophys. Acta 67, 104-137).