Characterization of the cellular signaling induced by the endoplasmic reticulum (ER) stress in isolated perfused rat hearts and its possible impact on tissue injury

ROMÁN B; VITTONE L; SALAS M; MUNDIÑA -WEILENMANN C.; MARIÁNGELO JIE; SAID M

Río de Janeiro

Congreso; IUPS 38th World Congress; 2017

International Union of Physiological Sciences IUPS

A variety of diseases challenge the endoplasmic reticulum protein folding capacity. Protein misfolding activates the ER stress response, a conserved three-branch signaling system (ATF6, IRE1alpha and PERK) that triggers multiple processes that initially restore ER function: ATF6 induces the transcription of XBP1 and GRP78 (the main ER chaperone that promotes protein folding); IRE1alpha activation produces the splicing of XBP1 (sXBP1) which also increases the expression of GRP78 and PERK pathway attenuates protein synthesis. If ER stress is severe or prolonged, PERK and IRE1alpha may lead to cell death. The objective of this work was to characterize the cellular signaling induced by the ER stress in isolated perfused rat hearts subjected to Ischemia/Reperfusion (I 30 min/R 60 min) and to evaluate its impact on tissue injury. We assessed mRNA expression of GRP78, total XBP1, sXBP1 and GAPDH as a housekeeping gene (real time qRT-PCR) at 60 min R in the absence or the presence of the chemical chaperone 4-phenylbutyric acid (4-PBA, 3mM). The levels of mRNA of GRP78, total XBP1 and sXBP1 were increased with respect to control hearts (1.69±0.12, 1.53±0.08 and 2.73±0.22 fold change respectively, n=7-10, p