Alcoholism, clinical and experimental research
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Alcohol. Clin. Exp. Res. · Feb 2014
Activation of the epithelial-to-mesenchymal transition factor snail mediates acetaldehyde-induced intestinal epithelial barrier disruption.
Acetaldehyde (AcH) is mutagenic and can reach high concentrations in colonic lumen after ethanol consumption and is associated with intestinal barrier dysfunction and an increased risk of progressive cancers, including colorectal carcinoma. Snail, the transcription factor of epithelial-mesenchymal transition, is known to down-regulate expression of tight junction (TJ) and adherens junction (AJ) proteins, resulting in loss of epithelial integrity, cancer progression, and metastases. As AcH is mutagenic, the role of Snail in the AcH-induced disruption of intestinal epithelial TJs deserves further investigation. Our aim was to investigate the role of oxidative stress and Snail activation in AcH-induced barrier disruption in Caco-2 monolayers. ⋯ Our data demonstrate that oxidative stress-mediated Snail phosphorylation is likely a novel mechanism contributing to the deleterious effects of AcH on the TJ and AJ, and intestinal barrier function.
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Alcohol. Clin. Exp. Res. · Feb 2014
Prenatal alcohol exposure is associated with altered subcellular distribution of glucocorticoid and mineralocorticoid receptors in the adolescent mouse hippocampal formation.
Accumulating evidence indicates that several of the long-term consequences of prenatal alcohol exposure (PAE) are the result of changes in the development and function of cortico-limbic structures, including the hippocampal formation. The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are key regulators of hippocampal formation development, structure, and functioning and, thus, are potential mediators of PAE's effects on this brain region. In the present studies, we assessed the impact of PAE on components of corticosteroid signaling pathways in the mouse hippocampal formation. ⋯ The data support a model in which PAE leads to increased nuclear localization of GRs secondary to reductions in FKBP51 and increases in 11β-HSD1 levels in the adolescent mouse hippocampal formation. Persistent dysregulation of GR subcellular distribution is predicted to damage the hippocampal formation and may underlie many of the effects of PAE on hippocampal-dependent functioning.