MITOPHAGY AND ROS PRODUCTION DURING ACUTE PANCREATITIS

ROPOLO ALEJANDRO; QUARLERI JORGE; GRASSO DANIEL; VANASCO VIRGINIA; OJEDA DIEGO

Ciudad Autónoma de Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Sociedades Organizadoras: SAIC, SAIB, SAI, SAA, SAB, SAB, SAFE, SAFIS, SAH, SAP

Mitophagy, an autophagy pathway that selectively degrades damaged mitochondria, is an early cellular event in acute pancreatitis (AP). Mitochondria, as a source of ATP and other biological molecules, are necessary for autophagy; but are also the main cellular source of active O2 species (ROS). Both, ROS and nitric oxide (NO), could regulate autophagy during pancreatitis. The aim of this work was to analyze mitochondrial function and dynamics, and cellular redox state during AP in a cellular model. Experimental model: AR42J pancreatic acinar-cells were treated with 7.4uM caerulein (CAE) during 15, 30 and 60 min. Mitochondrial function was assessed by determining the mitochondrial inner membrane potential using the probe TMRM by flow cytometry. For mitochondrial dynamics, OPA1 (fusion protein) and DRP1 (fission protein) expressions were determined. Mitochondrial degradation by mitophagy was evaluated by transfecting cells with dual pMITO vector. Specific probes were used in order to study cellular production of H2O2, ROS, NO and mitochondrial O2-. Results: Mitochondrial potential was significantly decreased since 30 min (25% compared control cells, p < 0.01) in cells treated with CAE. DRP1 expression was increased after 30 min, whereas OPA 1 increased after 60 min of treatment (75% and 100% respectively compared to control cells, p