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Hydrogen peroxide inhibits Ca²⁺ efflux through plasma membrane Ca²⁺-ATPase in mouse parotid acinar cells
The Korean Journal of Physiology and Pharmacology ; : 215-223, 2018.
Article in English | WPRIM | ID: wpr-728620
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Perfusion / Plasma / Catalase / Inositol 1,4,5-Trisphosphate / Cell Membrane / Calcium / Reactive Oxygen Species / Cytosol / Extracellular Fluid / Dithiothreitol Limits: Animals Language: English Journal: The Korean Journal of Physiology and Pharmacology Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Perfusion / Plasma / Catalase / Inositol 1,4,5-Trisphosphate / Cell Membrane / Calcium / Reactive Oxygen Species / Cytosol / Extracellular Fluid / Dithiothreitol Limits: Animals Language: English Journal: The Korean Journal of Physiology and Pharmacology Year: 2018 Type: Article