4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast

Humeres, C.; Montenegro, J.; Varela, M.; Ayala, P; Vivar, R; Letelier, A; Olmedo, I; Catalán M.; Rivas, C; Baeza, P; Munoz, C; Garcia, L.; Lavandero S.; Diaz-Araya, G

Keywords: 4, Phenylbutyric acid; Cardiac fibroblast; ER stress; Thapsigargin

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. (C) 2014 Elsevier Ltd. All rights reserved.

Más información

Título según WOS: 4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast
Título según SCOPUS: 4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast
Título de la Revista: Toxicology in vitro : an international journal published in association with BIBRA.
Volumen: 28
Número: 8
Editorial: PERGAMON-ELSEVIER SCIENCE LTD
Fecha de publicación: 2014
Página de inicio: 1443
Página final: 1448
Idioma: English
DOI:

10.1016/j.tiv.2014.07.013

Notas: ISI, SCOPUS