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Article Abstract
Aim: Previous research in our laboratory found that a biologically active sphingomyelin metabolite, sphingosylphosphorylcholine (SPC), can inhibit myocardial cell apoptosis caused by ischemia with an unknown mechanism. Here, we aimed to study the possible participation of EPAS1 in the protection process of SPC.
Methods: The rat cardiomyocytes deprived of serum were used to mimic ischemic-caused apoptosis, then treated with or without SPC. The expression and nuclear shift of EPAS1 were detected by western blot and immunofluorescence, and its function was studied using its siRNA.
Key Finding: Our research shows that SPC inhibited serum starvation caused cardiomyocyte apoptosis, accompanied by the up-regulation and nucleus translocation of EPAS1. EPAS1 levels did not change when its transcript was blocked by Actinomycin D, which prompted us to search for a post-transcription mechanism for its increased expression, and finally found that miR-155-5p, regulated by STAT3, was a new post-transcription regulator to EPAS1. Further investigation found that EPAS1 participated in the protective effect of SPC is mainly achieved by activating the downstream target gene, interleukin-6 (IL-6).
Significance: Our results expand our understanding of the biological functions of SPC, and bring a new pathway as a potential therapeutic target to the treatment of cardiovascular diseases caused by myocardial apoptosis.
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| http://dx.doi.org/10.1016/j.lfs.2020.118692 | DOI Listing |
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