Hydrogen peroxide attenuates refilling of intracellular calcium store in mouse pancreatic acinar cells.
10.4196/kjpp.2017.21.2.233
- Author:
Mi Na YOON
1
;
Dong Kwan KIM
;
Se Hoon KIM
;
Hyung Seo PARK
Author Information
1. Department of Physiology, College of Medicine, Konyang University, Daejeon 35365, Korea. hspark@konyang.ac.kr
- Publication Type:Original Article
- Keywords:
Hydrogen peroxide;
Intracellular Ca²⁺ stores;
Pancreatic acinar cells;
Reactive oxygen species;
Sarcoplasmic reticulum Ca²⁺ ATPase
- MeSH:
Acinar Cells*;
Animals;
Antioxidants;
Calcium*;
Carbachol;
Catalase;
Cell Membrane;
Cytosol;
Extracellular Fluid;
Hydrogen Peroxide*;
Hydrogen*;
Ion Transport;
Mice*;
Pancreatitis;
Perfusion;
Reactive Oxygen Species;
Reticulum;
Ruthenium Red;
Thapsigargin
- From:The Korean Journal of Physiology and Pharmacology
2017;21(2):233-239
- CountryRepublic of Korea
- Language:English
-
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 H₂O₂ at 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, H₂O₂ still 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. H₂O₂ at 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 H₂O₂ in 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.
