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Atorvastatin inhibits GSK-3beta phosphorylation by cardiac hypertrophic stimuli.

  • Planavila A
  • Rodríguez-Calvo R
  • Palomer FX
  • Coll T
  • Sánchez RM
  • Merlos M
  • Laguna JC
  • Vazquez M
In this study we examined the effect of the statin atorvastatin on the Akt/GSK-3beta pathway. Our findings indicate that atorvastatin treatment for 15 days inhibited pressure overload-induced cardiac hypertrophy and prevented nuclear translocation of GATA4 and c-Jun and AP-1 DNA-binding activity. In addition, atorvastatin treatment prevented the increase in the phosphorylation of Akt and GSK-3beta caused by cardiac hypertrophy, and this effect correlated with an increase in protein levels of phosphatase and tensin homolog on chromosome 10 (PTEN), which negatively regulates the phosphoinositide-3 kinase/Akt pathway. To test whether the inhibitory effect of atorvastatin on Akt and GSK-3beta phosphorylation was direct we performed in vitro studies using embryonic rat heart-derived H9c2 cells, human AC16 cardiomyoblasts and neonatal rat cardiomyocytes. Preincubation of cells with atorvastatin prevented Akt/GSK-3beta phosphorylation by different hypertrophic stimuli without affecting PTEN protein levels. However, atorvastatin prevented endogenous reactive oxygen species (ROS) generation and PTEN oxidation, a process that correlates with its inactivation, suggesting that atorvastatin prevents ROS-induced PTEN inactivation in acute treatments. These findings point to a new potential anti-hypertrophic effect of statins, which can prevent activation of the Akt/GSK-3beta hypertrophic pathway by modulating PTEN activation by different mechanisms in chronic and acute treatments.

Increased production of the ether-lipid platelet-activating factor in intestinal epithelial cells infected by Salmonella enteritidis.

  • Egea L
  • Giménez R
  • Lúcia D
  • Modolell I
  • Badia J
  • Baldoma L
  • Aguilar J
When exposed to enteric pathogens intestinal epithelial cells produce several cytokines and other proinflammatory mediators. To date there is no evidence that the ether-lipid platelet-activating factor (PAF) is one of these mediators. Our results revealed a significant increase in PAF production by human colonic tissue 4 h after infection by enterohemorrhagic Escherichia coli (EHEC) or Salmonella enteritidis. PAF is produced in the gut by cells of the immune system in response to bacterial infection. To determine whether the epithelial cells of colonic mucosa might also modulate PAF levels, we carried out PAF quantification and analysis of the enzymes involved in PAF synthesis in 5-day-old (undifferentiated) or 28-day-old (differentiated) Caco-2 cell cultures. Infection of undifferentiated Caco-2 cells with either bacterium had no effect on PAF levels, whereas in differentiated cells, infection by S. enteritidis increased PAF levels. Following infection by S. enteritidis, there were no changes in the activity of dithiothreitol-insensitive choline phosphotransferase. However, the enzymes of the remodeling pathway cytosolic phospholipase A(2), which catalyzes the formation of the PAF precursor lysoPAF, and lysoPAF acetyltransferase, are activated in the infected epithelial cells. This response is Ca(2+)-dependent.

Reduced novelty-P3 associated with increased behavioral distractibility in schizophrenia.

  • Cortiñas M
  • Corral MJ
  • Garrido G
  • Garolera M
  • Pajares M
  • Escera C
Behavioral and electrophysiological brain responses were used to examine the relationship between the vulnerability to distraction and the orienting response in schizophrenia. Nineteen schizophrenics and nineteen matched healthy controls were instructed to ignore task-irrelevant auditory stimuli while they classified capital letters and digits. The auditory sequences contained repetitive standard tones occasionally replaced by complex novel sounds. Relative to controls, patients showed an increased behavioral distraction, as indicated by a larger response time increase caused by novel sounds, and a disturbance in the attention orienting toward distracting stimuli, as indicated by a reduced novelty-P3. This behavioral-electrophysiological dissociation may stem from a limited pool of available resources. Thus, the few attentional resources directed toward novel stimuli would be sufficient to cause an important decrease of the similarly reduced amount of resources assigned to task-relevant stimuli, resulting in a striking impairment of the ongoing task performance.

Electrophysiological and behavioral evidence of gender differences in the modulation of distraction by the emotional context.

  • Garcia-Garcia M
  • Domínguez-Borràs J
  • San-Miguel I
  • Escera C
Gender differences in brain activity while processing emotional stimuli have been demonstrated by neuroimaging and electrophysiological studies. However, the possible differential effects of emotion on attentional mechanisms between women and men are less understood. The present study aims to elucidate any gender differences in the modulation of unexpected auditory stimulus processing using an emotional context elicited by aversive images. Fourteen men and fourteen women performed a well-established auditory-visual distraction paradigm in which distraction was elicited by novel stimuli within a neutral or negative emotional context induced by images from the IAPS. Response time increased after unexpected novel sounds as a behavioral effect of distraction, and this increase was larger for women, but not for men, within the negative emotional context. Novelty-P3 was also modulated by the emotional context for women but not for men. These results reveal stronger novelty processing in women than in men during a threatening situation.

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  • Institut de Cultura de Barcelona
  • Ciudades y Gobiernos Locales Unidos
Podeu consultar la versió en ucraïnès a: http://hdl.handle.net/11703/111577Podeu consultar la versió en català a: http://hdl.handle.net/11703/90414, Podeu consultar la versió en castellà a: http://hdl.handle.net/11703/111352, Podeu consultar la versió en francès a: http://hdl.handle.net/11703/111513, Podeu consultar la versió en anglès a: http://hdl.handle.net/11703/111517, Podeu consultar la versió en àrab a: http://hdl.handle.net/11703/111519, Podeu consultar la versió en búlgar a: http://hdl.handle.net/11703/111521, Podeu consultar la versió en alemany a: http://hdl.handle.net/11703/111566, Podeu consultar la versió en gallec a: http://hdl.handle.net/11703/111567, Podeu consultar la versió en italià a: http://hdl.handle.net/11703/111568, Podeu consultar la versió en japonès a: http://hdl.handle.net/11703/111569, Podeu consultar la versió en persa a: http://hdl.handle.net/11703/111570, Podeu consultar la versió en portuguès a: http://hdl.handle.net/11703/111571, Podeu consultar la versió en serbi a: http://hdl.handle.net/11703/111572, Podeu consultar la versió en suec a: http://hdl.handle.net/11703/111574

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