title: 4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast.
abstract: Cardiac fibroblast (CF) survival is important for the maintenance of the extracellular matrix homeostasis in the heart; providing a functional support to cardiomyocytes necessary for the correct myocardial function. Endoplasmic reticulum (ER) stress causes cellular dysfunction and cell death by apoptosis; and thapsigargin is a well-known ER stress inducer. On the other hand, the chemical chaperone, 4-phenylbutyric acid (4-PBA) had showed to prevent ER stress; however, in cardiac fibroblast both the ER stress induced by thapsigargin and prevention by 4-PBA, have not been studied in detail. Neonate rat CF were treated with thapsigargin in presence or absence of 4-PBA, and cell viability was evaluated by trypan blue exclusion and apoptosis by flow cytometry; whereas CHOP, BIP, PDI, ATF4 and procollagen protein levels were assessed by western blot. In CF, thapsigargin triggered the unfolded protein response detected by early increases in ATF4, CHOP, PDI and BIP protein levels as well as, the accumulation of intracellular procollagen. Thapsigargin also stimulated CF death in a time and concentration-dependent manner. ER stress, CF death and apoptosis induced by thapsigargin were prevented by 4-PBA. Conclusion our data suggest that 4-PBA prevent ER stress, intracellular procollagen accumulation, CF death and apoptosis induced by thapsigargin.
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Humeres
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Montenegro
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Varela
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Ayala
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Vivar
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Letelier
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: I
authors.initials: I
authors.lastname: Olmedo
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Catalán
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Rivas
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Baeza
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: García
authors.affiliation: Centro FONDAP ACCDis (Advanced Center of Chronic Diseases), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: S
authors.initials: S
authors.lastname: Lavandero
authors.affiliation: Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile; Centro FONDAP ACCDis (Advanced Center of Chronic Diseases), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile. Electronic address: gadiaz@ciq.uchile.cl.
authors.forename: G
authors.initials: G
authors.lastname: Díaz-Araya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology; D010654:Phenylbutyrates / Q000494:pharmacology*; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000633:toxicity*; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D010654:Phenylbutyrates; D011347:Procollagen; D019284:Thapsigargin; C075773:4-phenylbutyric acid
keywords: 4-Phenylbutyric acid; Cardiac fibroblast; ER stress; Thapsigargin