title: Ursodeoxycholic and deoxycholic acids: Differential effects on intestinal Ca(2+) uptake, apoptosis and autophagy of rat intestine.
abstract: The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca(2+) uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca(2+) uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca(2+) uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca(2+) absorption occur by decreasing the Ca(2+) uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca(2+) uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca(2+) pathway.
authors.affiliation: Laboratorio "Dr. Fernando Cañas", Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Pabellón Argentina, 2do. Piso, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Rodríguez
authors.affiliation: Laboratorio "Dr. Fernando Cañas", Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Pabellón Argentina, 2do. Piso, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Rivoira
authors.affiliation: Laboratorio "Dr. Fernando Cañas", Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Pabellón Argentina, 2do. Piso, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Adriana del V
authors.initials: Adel V
authors.lastname: Pérez
authors.affiliation: Laboratorio "Dr. Fernando Cañas", Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Pabellón Argentina, 2do. Piso, Ciudad Universitaria, 5000 Córdoba, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Marchionatti
authors.affiliation: Laboratorio "Dr. Fernando Cañas", Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Pabellón Argentina, 2do. Piso, Ciudad Universitaria, 5000 Córdoba, Argentina. Electronic address: ntolosatalamoni@yahoo.com.ar.
authors.forename: Nori G
authors.initials: NG
authors.lastname: Tolosa de Talamoni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
chemical_list: D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; D002118:Calcium
keywords: Apoptosis; Autophagy; Ca(2+) uptake; NO; NaDOC; UDCA