Pancreatic mitochondrial bioenergetics in an animal model of acute pancreatitis

VANASCO VIRGINIA; MARCHINI TIMOTEO; MAGNANI NATALIA; ALVAREZ SILVIA; VACCARO MARÍA INÉS

Buenos Aires

Conferencia; Conferences Buenos Aires 2013 Autophagy: Biology and Disease; 2013

Facultad de Farmacia y Bioquímica - CONICET

An alteration in the autophagic flux or a defect in the selective autophagy of secretory granules (zymophagy) during Acute pancreatitis (AP), promotes cell damage and the progression to a severe disease (JBC 2011). ATP and other molecules necessary in autophagy process are provided by mitochondria, so a normal mitochondrial bioenergetics would be necessary for maintaining the autophagic process in response to the disease. The aim of this study was to analyze mitochondrial bioenergetics and its relationship with the autophagic process in an experimental model of severe AP. Female Sprague-Dawley rats (45 days old) were ip injected with caerulein (CAE) 50 mg/kg ip 1h intervals. Treated groups were studied: CAE 1, animals injected with a single dose and then sacrificed 1h; CAE 3, animals injected with 3 doses and sacrificed at 3h; CAE 24, animals injected with 6 doses and sacrificed at 24 h. Simultaneously with each CAE group, control groups (CG) were performed using the same protocol but injected with vehicle. CAE 3 and CAE 24 animals show mitochondrial O2 consumption in state 3 decreased by 30 and 40% respectively (CG: 40 ± 5 ng-atO/min.mg prot). These results are reflected in a decrease in mitochondrial respiratory control. ATP production was observed for all CAE groups decreased, and this difference was greater in CAE3 group (CG: 140 ± 18 nmol ATP/ min.mg.prot, P < 0.01). These results demonstrate that mitochondrial bioenergetic profile is impaired early during experimental AP, which may affect zymography flux leading to the cell damage characteristic of the severe disease.