Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A(2)-dependent mechanism.

American Journal of Physiology. Cell Physiology
Kiyoshi ItagakiPer-Olof Hasselgren

Abstract

Muscle wasting in various catabolic conditions is at least in part regulated by glucocorticoids. Increased calcium levels have been reported in atrophying muscle. Mechanisms regulating calcium homeostasis in muscle wasting, in particular the role of glucocorticoids, are poorly understood. Here we tested the hypothesis that glucocorticoids increase intracellular calcium concentrations in skeletal muscle and stimulate store-operated calcium entry (SOCE) and that these effects of glucocorticoids may at least in part be responsible for glucocorticoid-induced protein degradation. Treatment of cultured myotubes with dexamethasone, a frequently used in vitro model of muscle wasting, resulted in increased intracellular calcium concentrations determined by fura-2 AM fluorescence measurements. When SOCE was measured by using calcium "add-back" to muscle cells after depletion of intracellular calcium stores, results showed that SOCE was increased 15-25% by dexamethasone and that this response to dexamethasone was inhibited by the store-operated calcium channel blocker BTP2. Dexamethasone treatment stimulated the activity of calcium-independent phospholipase A(2) (iPLA(2)), and dexamethasone-induced increase in SOCE was reduced by the iPLA...Continue Reading

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Citations

May 18, 2010·Current Opinion in Clinical Nutrition and Metabolic Care·Per-Olof HasselgrenSteven Tizio
Apr 9, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Susan D KranerMark M Rich
Sep 29, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Nima AlamdariPer-Olof Hasselgren
Mar 6, 2016·Journal of Physiology and Biochemistry·Cigdem Selli, Metiner Tosun
Nov 10, 2012·Journal of Receptor and Signal Transduction Research·Chung-Pin LiuChung-Ren Jan
Jul 27, 2017·Molecular and Cellular Biochemistry·Michele MenottaMauro Magnani
Jan 4, 2019·International Journal of Oral Science·Yuichiro KusudaRyuji Hosokawa
Nov 2, 2020·Molecular and Cellular Endocrinology·Chinmayee DasMathilakath M Vijayan
Oct 27, 2020·Journal of Neuromuscular Diseases·Mattia QuattrocelliElizabeth M McNally
May 7, 2021·Scientific Reports·Chinmayee DasMathilakath M Vijayan

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