Molecular mechanisms involved in the enhancement of mitochondrial malate dehydrogenase activity by calcitriol in chick intestine

• Autores: Perez, Adriana del Valle; Centeno, Viviana Andrea; Tolosa, Nori Graciela
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Mitochondria; Malate; Calcitriol
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Mitochondrial malate dehydrogenase (mMDH) from intestine is the NAD-linked oxidoreductase of the tricarboxylic acid cycle with the highest activity and response to vitamin D treatment in vitamin D deficient chicks (-D). The aim of this study was to elucidate potential molecular mechanisms by which cholecalciferol or calcitriol enhances the activity of this enzyme. One group of animals used was composed of ?D and ?D treated with cholecalciferol or with calcitriol. A second group consisted of ?D and ?D supplemented with high Ca2+ diet. A third group included chicks receiving either a normal or a low Ca2+ diet. In some experiments, animals were injected with cycloheximide. Data showed that either vitamin D (cholecalciferol or calcitriol) or a low Ca2+ diet increases mMDH activity. High Ca2+ diet did not modify the intestinal mMDH activity from -D. The mMDH activity from ?D remained unaltered when duodenal cells were exposed to 10-8 mol/L calcitriol for 15 min. The enhancement of mMDH activity by calcitriol was completely abolished by simultaneous cycloheximide injection to -D. mMDH mRNA levels, detected by RT-PCR, indicate that calcitriol did not affect gene expression. In contrast, Western blots show that calcitriol enhanced the protein expression. In conclusion, calcitriol stimulates intestinal mMDH activity by increasing protein synthesis. No response of mMDH activity by rapid effects of calcitriol or activation through increment of serum Ca2+ was demonstrated. Consequently, ATP production would be increased facilitating the Ca2+ exit from the enterocytes via Ca2+-ATPase and Na+/Ca2+ exchanger, which participate in the intestinal Ca2+ absorption.
Fil: Perez, Adriana del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Bioquímica y Biología Molecular; Argentina
Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Bioquímica y Biología Molecular; Argentina
Fil: Tolosa, Nori Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina