Phosphorylation and subcellular localization of Na+/H+ exchanger isoform 3 (NHE3) are associated with altered gallbladder absorptive function after formation of cholesterol gallstones

Na+/H+ exchanger isoform 3 (NHE3) dysfunction is thought to contribute to the altered gallbladder absorption that occurs in cholesterol gallstone disease, but the mechanism is unknown. The current study was undertaken to examine the expression, phosphorylation, and subcellular localization of NHE3 in gallbladder epithelium cells (GBECs) of male C57BL/6 mice on a control or lithogenic diet. Thirty-six 8-week-old male C57BL/6 mice were randomly assigned to receive a high cholesterol diet or a regular diet for 8 weeks. Gallstone formation was recorded. Gallbladder bile cholesterol, phospholipid, and total bile acids were examined. RT-PCR was used to measure NHE3 mRNA expression. NHE3 protein expression and subcellular localization were examined by Western blotting and immunofluorescence microscopy, respectively. Gallstones were formed in all mice fed the lithogenic diet. Despite higher NHE3 mRNA expression in gallbladders of the mice on the lithogenic diet than in those on the control diet, there was no significant difference in expression of total NHE3 protein. However, a higher level of NHE3 phosphorylated at serine-552 (P-NHE3) was seen on the lithogenic diet. In immunofluorescence studies, NHE3 protein was expressed both on the apical membrane and in the cytoplasm of mouse GBEC. This pattern of subcellular distribution of NHE3 strongly corroborates an exchanger trafficking mechanism in NHE3 activity regulation in mouse GBEC. We conclude that increased phosphorylation of NHE3 following gallstone formation leads to turnover of the exchanger, resulting in decreased gallbladder concentrating function (AU)

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Abordaje metabólico en las encefalopatía epilépticas del lactante / Metabolic approach in epileptic encephalopathies in infants

Introducción. Aunque la incidencia global de los errores congénitos del metabolismo es baja, su diagnóstico precoz es fundamental, ya que algunos de ellos tienen tratamiento específico. Desarrollo. Se revisan los principales errores congénitos del metabolismo tratables que pueden cursar como encefalopatía epiléptica de inicio precoz, así como sus marcadores bioquímicos y su tratamiento. Conclusiones. Es importante pensar en la posibilidad de un error congénito del metabolismo con terapia específica, ya que es fundamental que ésta comience lo antes posible para evitar un daño neurológico permanente (AU)

Introduction. Although the overall incidence of inborn errors of metabolism is low, their early diagnosis is essential, since some of them have a specific treatment. Development. We review the main treatable inborn errors of metabolism that can present as early-onset epileptic encephalopathies, together with their biochemical markers and their treatment. Conclusions. It is important to think about the possibility of an inborn error of metabolism with a specific therapy, since it is crucial for this to be started as soon as possible in order to prevent permanent neurological damage (AU)