title: Hydrogen peroxide attenuates refilling of intracellular calcium store in mouse pancreatic acinar cells.
abstract: Intracellular calcium (Ca2+) oscillation is an initial event in digestive enzyme secretion of pancreatic acinar cells. Reactive oxygen species are known to be associated with a variety of oxidative stress-induced cellular disorders including pancreatitis. In this study, we investigated the effect of hydrogen peroxide (H2O2) on intracellular Ca2+accumulation in mouse pancreatic acinar cells. Perfusion of H2O2at 300 µM resulted in additional elevation of intracellular Ca2+levels and termination of oscillatory Ca2+signals induced by carbamylcholine (CCh) in the presence of normal extracellular Ca2+. Antioxidants, catalase or DTT, completely prevented H2O2-induced additional Ca2+increase and termination of Ca2+oscillation. In Ca2+-free medium, H2O2still enhanced CCh-induced intracellular Ca2+levels and thapsigargin (TG) mimicked H2O2-induced cytosolic Ca2+increase. Furthermore, H2O2-induced elevation of intracellular Ca2+levels was abolished under sarco/endoplasmic reticulum Ca2+ATPase-inactivated condition by TG pretreatment with CCh. H2O2at 300 µM failed to affect store-operated Ca2+entry or Ca2+extrusion through plasma membrane. Additionally, ruthenium red, a mitochondrial Ca2+uniporter blocker, failed to attenuate H2O2-induced intracellular Ca2+elevation. These results provide evidence that excessive generation of H2O2in pathological conditions could accumulate intracellular Ca2+by attenuating refilling of internal Ca2+stores rather than by inhibiting Ca2+extrusion to extracellular fluid or enhancing Ca2+mobilization from extracellular medium in mouse pancreatic acinar cells.
authors.affiliation: Department of Physiology, College of Medicine, Konyang University, Daejeon 35365, Korea.
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Yoon
authors.affiliation: Department of Physiology, College of Medicine, Konyang University, Daejeon 35365, Korea.
authors.forename: Dong Kwan
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Konyang University, Daejeon 35365, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Konyang University, Daejeon 35365, Korea.; Myunggok Medical Research Institute, Konyang University, Daejeon 35365, Korea.
authors.forename: Hyung Seo
authors.initials: HS
authors.lastname: Park
keywords: Hydrogen peroxide; Intracellular Ca2+ stores; Pancreatic acinar cells; Reactive oxygen species; Sarcoplasmic reticulum Ca2+ ATPase