CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Characterization of the cellular signaling induced by the endoplasmic reticulum (ER) stress in isolated perfused rat hearts and its possible impact on tissue injury.
Autor/es:
JUAN IGNACIO MARIANGELO; LETICIA B. VITTONE; MARGARITA SALAS; CECILIA MUNDIÑA-WEILENMANN; BARBARA S. ROMAN; MATILDE SAID
Lugar:
Rio de Janeiro
Reunión:
Congreso; XXXVIII IUPS Congress; 2017
Institución organizadora:
International Union of Physiological Sciences (IUPS)
Resumen:
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, IRE1 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); IRE1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 IRE1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-phenylbutiric 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