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- Title
Multi-Staged Regulation of Lipid Signaling Mediators during Myogenesis by COX-1/2 Pathways.
- Authors
Mo, Chenglin; Wang, Zhiying; Bonewald, Lynda; Brotto, Marco
- Abstract
Cyclooxygenases (COXs), including COX-1 and -2, are enzymes essential for lipid mediator (LMs) syntheses from arachidonic acid (AA), such as prostaglandins (PGs). Furthermore, COXs could interplay with other enzymes such as lipoxygenases (LOXs) and cytochrome P450s (CYPs) to regulate the signaling of LMs. In this study, to comprehensively analyze the function of COX-1 and -2 in regulating the signaling of bioactive LMs in skeletal muscle, mouse primary myoblasts and C2C12 cells were transfected with specific COX-1 and -2 siRNAs, followed by targeted lipidomic analysis and customized quantitative PCR gene array analysis. Knocking down COXs, particularly COX-1, significantly reduced the release of PGs from muscle cells, especially PGE2 and PGF2α, as well as oleoylethanolamide (OEA) and arachidonoylethanolamine (AEA). Moreover, COXs could interplay with LOXs to regulate the signaling of hydroxyeicosatetraenoic acids (HETEs). The changes in LMs are associated with the expression of genes, such as Itrp1 (calcium signaling) and Myh7 (myogenic differentiation), in skeletal muscle. In conclusion, both COX-1 and -2 contribute to LMs production during myogenesis in vitro, and COXs could interact with LOXs during this process. These interactions and the fine-tuning of the levels of these LMs are most likely important for skeletal muscle myogenesis, and potentially, muscle repair and regeneration.
- Subjects
MYOBLASTS; MYOGENESIS; SKELETAL muscle; ARACHIDONIC acid; LIPIDS; MUSCLE cells
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 18, p4326
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20184326