title: Cardiotrophin-1 decreases liver apoptosis through calpastatin induction.
abstract: BACKGROUND
  Cardiotrophin-1 (CT1) has been used to prevent cell death in different models of liver injury in rats. D-galactosamine induces cell death in culture rat and human hepatocytes. The present study evaluated the cytoprotective effects of CT1 in an experimental model of apoptosis induced by D-galactosamine in hepatocytes.
  
  
  METHODS
  DNA fragmentation, calpain activity and Western blots of caspase-3, calpastatin and Stat3, and Akt phosphorylation were measured. Stat3 and Akt inhibitors were used to analyze the mechanisms of action of CT1.
  
  
  RESULTS
  CT1 caused an increase in Stat3 and Akt phosphorylation and a decrease of DNA fragmentation, calpain activity, and caspase-3 induced by D-galactosamine. The reduction of calpain activity by CT1 was associated with an increase of calpastatin (its endogenous inhibitor). The effects of CT1 were also dependent on the activation of Sta3 or Akt.
  
  
  CONCLUSIONS
  CT1 decreases cell death through a mechanism related to Stat3 and Akt phosphorylation and activation of calpastatin in D-galactosamine-treated hepatocytes.
authors.affiliation: Instituto Maimónides para la Investigación Biomédica (IMIBIC). Hospital Reina Sofia, Universidad de Cordoba, Cordoba, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Herencia
authors.affiliation: Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University, Hospital/University of Cordoba, Cordoba, Spain; CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: yolandaalmaden@yahoo.es.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Almadén
authors.affiliation: Instituto Maimónides para la Investigación Biomédica (IMIBIC). Hospital Reina Sofia, Universidad de Cordoba, Cordoba, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ferrín
authors.affiliation: Departamento de Biología Experimental, Universidad de Jaén, Jaén, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Martínez-Romero
authors.affiliation: Instituto Maimónides para la Investigación Biomédica (IMIBIC). Hospital Reina Sofia, Universidad de Cordoba, Cordoba, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: de la Mata
authors.affiliation: Departamento de Cirugía General y Digestiva, Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Ciria
authors.affiliation: Departamento de Cirugía General y Digestiva, Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Briceño
authors.affiliation: Instituto Maimónides para la Investigación Biomédica (IMIBIC). Hospital Reina Sofia, Universidad de Cordoba, Cordoba, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Juan Rafael
authors.initials: JR
authors.lastname: Muñoz-Castañeda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D005688:Galactosamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013552:Swine
chemical_list: D002135:Calcium-Binding Proteins; D016207:Cytokines; D050796:STAT3 Transcription Factor; D005688:Galactosamine; C033668:calpastatin; C092073:cardiotrophin 1; D051057:Proto-Oncogene Proteins c-akt; D002154:Calpain; D053148:Caspase 3
keywords: Akt; Apoptosis; Calpain; Calpastatin; Cardiotrophin-1; Hepatocytes; Stat3