Effect of H2O2 on CCK-8-evoked changes in mitochondrial activity in isolated mouse pancreatic acinar cells

Background information. This paper studies the effect of H2O2 on mitochondrial responses evoked by CCK-8 (cholecystokinin 8) in mouse pancreatic acinar cells. Cytosolic ([Ca2+]c) and mitochondrial ([Ca2+]m) free-calcium concentrations, mitochondrial inner membrane potential ((psi)m) and FAD autofluorescence were monitored using confocal laser scanning microscopy. Results. CCK-8 induced an increase in [Ca2+]m that slowly declined towards the prestimulation level. Depolarization of (psi)m that partially recovered, as well as increases in FAD autofluorescence, could also be observed in response to the hormone. Pretreatment of cells with 1 mM H2O2 alone resulted in marked changes in mitochondrial parameters and, moreover, H2O2 inhibited the CCK-8-evoked changes in [Ca2+]m, (psi)m and FAD autofluorescence. The results of the present study have demonstrated that CCK-8 can evoke marked changes in pancreatic acinar cell mitochondrial activity and that CCK-8-evoked responses are blocked by H2O2. Additionally, H2O2 releases Ca2+ from intracellular stores and inhibits pancreatic acinar cell responses to CCK-8. Conclusion. The effects observed reflect an impairment of mitochondrial activity in the presence of H2O2 that could represent some of its mechanisms of action to induce cellular damage leading to cell dysfunction and generation of pathologies.