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.
Highlights
Skeletal muscle myogenesis, such as muscle regeneration after injury, is a biological process critical for maintaining a functional musculoskeletal system
Our results indicated that co-treatment with PGE2 or 15-hydroxyeicosatetraenoic acids (HETEs), but not 12-HETE, partially recovered the inhibition of both siRNAs used against COX-1 or -2 on myogenic differentiation
Following the studies of primary myoblasts, lipidomic analysis was performed in C2C12 cells
Summary
Skeletal muscle myogenesis, such as muscle regeneration after injury, is a biological process critical for maintaining a functional musculoskeletal system. Myogenesis generally consists of several consecutive stages, including activation of satellite cells, proliferation of myoblasts, myogenic differentiation, and fusion into multinucleated myocytes that can later become fully mature and long, differentiated muscle cells, sometimes referred to as muscle fibers [1]. This process is highly coordinated, and many factors have been shown to be involved in the regulation of myogenesis [2]. PGE2 has been shown to enhance myoblast proliferation and differentiation [4,7], and PGF2α is able to promote muscle cell survival and fusion [8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
