Examinando por Autor "Molina, A."
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Ítem Catabolic Signaling Pathways, Atrogenes, and Ubiquitinated Proteins Are Regulated by the Nutritional Status in the Muscle of the Fine Flounder(Public Library of Science (PLoS), 2012-09) Fuentes, E.; Ruiz, P.; Valdes, J.; Molina, A.A description of the intracellular mechanisms that modulate skeletal muscle atrophy in early vertebrates is still lacking. In this context, we used the fine flounder, a unique and intriguing fish model, which exhibits remarkably slow growth due to low production of muscle-derived IGF-I, a key growth factor that has been widely acknowledged to prevent and revert muscle atrophy. Key components of the atrophy system were examined in this species using a detailed time-course of sampling points, including two contrasting nutritional periods. Under basal conditions high amounts of the atrogenes MuRF-1 and Atrogin-1 were observed. During fasting, the activation of the P38/MAPK and Akt/FoxO signaling pathways decreased; whereas, the activation of the IκBα/NFκB pathway increased. These changes in signal transduction activation were concomitant with a strong increase in MuRF-1, Atrogin-1, and protein ubiquitination. During short-term refeeding, the P38/MAPK and Akt/FoxO signaling pathways were strongly activated, whereas the activation of the IκBα/NFκB pathway decreased significantly. The expression of both atrogenes, as well as the ubiquitination of proteins, dropped significantly during the first hour of refeeding, indicating a strong anti-atrophic condition during the onset of refeeding. During long-term refeeding, Akt remained activated at higher than basal levels until the end of refeeding, and Atrogin-1 expression remained significantly lower during this period. This study shows that the components of the atrophy system in skeletal muscle appeared early in the evolution of vertebrates and some mechanisms have been conserved, whereas others have not. These results represent an important achievement for the area of fish muscle physiology, showing an integrative view of the atrophy system in a non-mammalian species and contributing to novel insights on the molecular basis of muscle growth regulation in earlier vertebrates.Ítem Correction: Catabolic Signaling Pathways, Atrogenes, and Ubiquitinated Proteins Are Regulated by the Nutritional Status in the Muscle of the Fine Flounder(Public Library of Science (PLoS), 2020-12) Fuentes, E.; Ruiz, P.; Valdes, J.; Molina, A.A description of the intracellular mechanisms that modulate skeletal muscle atrophy in early vertebrates is still lacking. In this context, we used the fine flounder, a unique and intriguing fish model, which exhibits remarkably slow growth due to low production of muscle-derived IGF-I, a key growth factor that has been widely acknowledged to prevent and revert muscle atrophy. Key components of the atrophy system were examined in this species using a detailed time-course of sampling points, including two contrasting nutritional periods. Under basal conditions high amounts of the atrogenes MuRF-1 and Atrogin-1 were observed. During fasting, the activation of the P38/MAPK and Akt/FoxO signaling pathways decreased; whereas, the activation of the IκBα/NFκB pathway increased. These changes in signal transduction activation were concomitant with a strong increase in MuRF-1, Atrogin-1, and protein ubiquitination. During short-term refeeding, the P38/MAPK and Akt/FoxO signaling pathways were strongly activated, whereas the activation of the IκBα/NFκB pathway decreased significantly. The expression of both atrogenes, as well as the ubiquitination of proteins, dropped significantly during the first hour of refeeding, indicating a strong anti-atrophic condition during the onset of refeeding. During long-term refeeding, Akt remained activated at higher than basal levels until the end of refeeding, and Atrogin-1 expression remained significantly lower during this period. This study shows that the components of the atrophy system in skeletal muscle appeared early in the evolution of vertebrates and some mechanisms have been conserved, whereas others have not. These results represent an important achievement for the area of fish muscle physiology, showing an integrative view of the atrophy system in a non-mammalian species and contributing to novel insights on the molecular basis of muscle growth regulation in earlier vertebrates.Ítem Epigenetic regulation of the ribosomal cistron seasonally modulates enrichment of H2A.Z and H2A.Zub in response to different environmental inputs in carp (Cyprinus carpio)(BMC, 2013-07) Simonet, N.; Reyes, M.; Nardocci, G.; Molina, A.; Alvarez, M.Background: The specific deposition of histone variants into chromatin is an important epigenetic mechanism that contributes to gene regulation through chromatin architectural changes. The histone variant H2A.Z is essential in higher eukaryotes, and its incorporation within chromatin is a relevant process for gene expression and genome stability. However, the dual positive and negative roles of H2A.Z in gene regulation still remain unclear. We previously reported that acclimatization in common carp fish (Cyprinus carpio) involves cyclical seasonal gene reprogramming as an adaptation response to its natural environment, when rRNA synthesis and processing are profoundly affected. Epigenetic mechanisms primarily contribute to the transcriptional modulation of ribosomal genes concomitant with the acclimatization process, thus significantly regulating this process. The aim of this study was to describe the presence of several H2A.Z subtypes in carp, and assess the role of H2A.Z on the ribosomal cistron in summer- and winter-acclimatized carp. Results: This paper reports for the first time about the transcriptional expression of four different H2A.Z subtypes belonging to the same organism. Remarkably, a novel H2A.Z.7 was found, which corresponds to a tissue-specific histone subtype that contains seven amino acid residues longer than the canonical H2A.Z. Moreover, H2A.Z enrichment through the ribosomal cistron was significantly higher during summer, when rRNA transcription and processing are highly active, than it was in winter. Similar patterns of H2A.Z enrichment are found in two seasonally active promoters for genes transcribed by RNA polymerase II, the L41 and Δ9- desaturase genes. Interestingly, ubiquitylated-H2A.Z (H2A.Zub) was strongly enriched on regulatory regions of the ribosomal cistron in summer-acclimatized carp. Additionally, H2A.Z was present in both heterochromatin and euchromatin states on ribosomal cistron and RNA polymerase II promoters. Conclusions: Our study revealed seasonally-dependent H2A.Z enrichment for active ribosomal cistron and RNA polymerase II promoters during the carp environmental adaptation. Moreover, seasonal H2A.Zub enrichment appears as a specific mechanism contributing to the regulation of chromatin architecture under natural conditions. The existence of several H2A.Z subtypes in carp suggests that the epigenetic regulation in this species constitutes a complex and finely tuned mechanism developed to cope with seasonal environmental changes that occur in its habitat.Ítem Gene structure of the carp fish ribosomal protein L41: Seasonally regulated expression(Elsevier Science, 2002-07) Molina, A.; Corta, A.; Martin, R.; Alvarez, M.; Burzio, L.; Krauskopf, M.; Vera, M.The seasonal acclimatization of the carp fish demands physiological compensatory responses. The process involves profound nucleolar adjustments and remarkable changes in rRNA synthesis, which affect ribosomal biogenesis. We have documented that protein kinase CK2, whose activity is related to ribosomal protein L41 and the regulation of rRNA synthesis, was expressed in notably higher amounts in summer-acclimatized carp compared to the cold-season adapted fish. Thus, we approached the study of the functional genomics of carp L41 protein. We report the first cloning of a fish L41 gene encoding the highly conserved 25 amino acids, including approximately 1700 bp regulatory upstream region and the 3′ polyadenylation signal, plus the isolation and characterization of two different L41 cDNAs. We found a clear differential expression of L41, which follows the same pattern as protein kinase CK2β that transcribes at higher levels in the summer-acclimatized carp than it does in the winter-adapted fish.Ítem Seasonal environmental changes regulate the expression of the histone variant macroH2A in an eurythermal fish(Elsevier [Former Publisher] Federation of European Biochemical Societies [Associate Organisation] Wiley [Commercial Publisher], 2005-10) Pinto, R.; Ivaldi, C.; Reyes, M.; Doyen, C.; Mietton, F.; Mongelard, F.; Alvarez, M.; Molina, A.; Dimitrov, S.; Krauskopf, M.; Vera, M.; Bouvet, P.Adaptation to cold and warm conditions requires dramatic change in gene expression. The acclimatization process of the common carp Cyprinus carpio L. in its natural habitat has been used to study how organisms respond to natural environmental changes. At the cellular level, adaptation to cold condition is accompanied by a dramatic alteration in nucleolar structure and a down regulation of the expression of ribosomal genes. We show that the enrichment of condensed chromatin in winter adapted cells is not correlated with an increase of the heterochromatin marker trimethyl and monomethyl K20H4. However, the expression of the tri methyl K4 H3 and of the variant histone macroH2A is significantly increased during the winter season together with a hypermethylation of CpG residues. Taking into account the properties of macroH2A toward chromatin structure and dynamics and its role in gene repression our data suggest that the increased expression of macroH2A and the hypermethylation of DNA which occurs upon winter-acclimatization plays a major role for the reorganization of chromatin structure and the regulation of gene expression during the physiological adaptation to a colder environment.Ítem Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and liver steatosis(Public Library of Science, 2017-04) Naour, S.; Espinoza, B.M.; Aedo, J.E.; Zuloaga, R.; Maldonado, J.; Bastias-Molina, M.; Silva, H.; Meneses, C.; Gallardo-Escarate, C.; Molina, A.; Valdés, J.A.Teleosts exhibit a broad divergence in their adaptive response to stress, depending on the magnitude, duration, and frequency of stressors and the species receiving the stimulus. We have previously reported that the red cusk-eel (Genypterus chilensis), an important marine farmed fish, shows a physiological response to stress that results in increased skeletal muscle atrophy mediated by over-expression of components of the ubiquitin proteasome and autophagy-lysosomal systems. To better understand the systemic effects of stress on the red cusk-eel metabolism, the present study assessed the transcriptomic hepatic response to repetitive handling-stress. Using high-Throughput RNA-seq, 259 up-regulated transcripts were found, mostly associated with angiogenesis, gluconeogenesis, and triacylglyceride catabolism. Conversely, 293 transcripts were down-regulated, associated to cholesterol biosynthesis, PPARα signaling, fatty acid biosynthesis, and glycolysis. This gene signature was concordant with hepatic metabolite levels and hepatic oxidative damage. Moreover, the increased plasmatic levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase) and AP (alkaline phosphatase), as well as liver histology suggest stress-induced liver steatosis. This study offers an integrative molecular and biochemical analysis of the hepatic response to handling-stress, and reveals unknown aspects of lipid metabolism in a non-model teleost.