Eva A Kuznetsova, Nikita S Fedorov, Guzel F Zakyrjanova, Artem I Malomouzh, Alexey M Petrov
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引用次数: 0
Abstract
Cholesterol is involved in the regulation of various signaling processes, and oxysterols are essential lipid messengers. The cholesterol derivative 25-hydroxycholesterol (25-HC) is overproduced by muscle macrophages in sarcopenia, myasthenia, and neurodegenerative diseases. Herein, we examined the effects of 25-HC on Ca2+ signaling and contractions of the mouse diaphragm, the main respiratory muscle. We found that 25-HC increased resting levels of cytosolic Ca2+ in muscle fibers. This effect was dependent on estrogen receptor α (ERα) and was mediated by Ca2+-efflux from intracellular stores via dantrolene-insensitive and TMB-8-sensitive channels, presumably inositol trisphosphate receptors (IP3Rs). In addition, 25-HC suppressed diaphragm contractile responses to direct stimulation of the muscle fibers. The negative effect of 25-HC on contraction force was inhibited by blockers of ERα and Ca2+ mobilization. Thus, 25-HC may suppress diaphragm muscle contractility due to activation of an ERα/IP3R/Ca2+in axis in muscle fibers. At the same time, 25-HC did not significantly modify the contractions elicited by phrenic nerve stimulation and respiratory activity in vivo. We discuss that the previously found enhancement of neuromuscular transmission mediated by 25-HC in the diaphragm can compensate for the reduction in the muscle contractions in the case of phrenic nerve activation.
期刊介绍:
Histochemistry and Cell Biology is devoted to the field of molecular histology and cell biology, publishing original articles dealing with the localization and identification of molecular components, metabolic activities and cell biological aspects of cells and tissues. Coverage extends to the development, application, and/or evaluation of methods and probes that can be used in the entire area of histochemistry and cell biology.