Hydrogen peroxide inhibits Ca²⁺ efflux through plasma membrane Ca²⁺-ATPase in mouse parotid acinar cells.
10.4196/kjpp.2018.22.2.215
- Author:
Min Jae KIM
1
;
Kyung Jin CHOI
;
Mi Na YOON
;
Sang Hwan OH
;
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:
Calcium;
Hydrogen peroxide;
Parotid acinar cells;
Plasma membrane calcium ATPase;
Reactive oxygen species
- MeSH:
Acinar Cells*;
Animals;
Antioxidants;
Calcium;
Catalase;
Cell Membrane*;
Cytosol;
Dithiothreitol;
Extracellular Fluid;
Hand;
Hydrogen Peroxide*;
Hydrogen*;
Inositol 1,4,5-Trisphosphate;
Ions;
Manganese;
Mice*;
Perfusion;
Plasma Membrane Calcium-Transporting ATPases;
Plasma*;
Reactive Oxygen Species
- From:The Korean Journal of Physiology and Pharmacology
2018;22(2):215-223
- CountryRepublic of Korea
- Language:English
-
Abstract:
Intracellular Ca²⁺ mobilization is closely linked with the initiation of salivary secretion in parotid acinar cells. Reactive oxygen species (ROS) are known to be related to a variety of oxidative stress-induced cellular disorders and believed to be involved in salivary impairments. In this study, we investigated the underlying mechanism of hydrogen peroxide (H₂O₂) on cytosolic Ca²⁺ accumulation in mouse parotid acinar cells. Intracellular Ca²⁺ levels were slowly elevated when 1 mM H₂O₂ was perfused in the presence of normal extracellular Ca²⁺. In a Ca²⁺-free medium, 1 mM H₂O₂ still enhanced the intracellular Ca²⁺ level. Ca²⁺ entry tested using manganese quenching technique was not affected by perfusion of 1 mM H₂O₂. On the other hand, 10 mM H₂O₂ induced more rapid Ca²⁺ accumulation and facilitated Ca²⁺ entry from extracellular fluid. Ca²⁺ refill into intracellular Ca²⁺ store and inositol 1,4,5-trisphosphate (1 µM)-induced Ca²⁺ release from Ca²⁺ store was not affected by 1 mM H₂O₂ in permeabilized cells. Ca²⁺ efflux through plasma membrane Ca²⁺-ATPase (PMCA) was markedly blocked by 1 mM H₂O₂ in thapsigargin-treated intact acinar cells. Antioxidants, either catalase or dithiothreitol, completely protected H₂O₂-induced Ca²⁺ accumulation through PMCA inactivation. From the above results, we suggest that excessive production of H₂O₂ under pathological conditions may lead to cytosolic Ca²⁺ accumulation and that the primary mechanism of H₂O₂-induced Ca²⁺ accumulation is likely to inhibit Ca²⁺ efflux through PMCA rather than mobilize Ca²⁺ ions from extracellular medium or intracellular stores in mouse parotid acinar cells.
