FTY720-P, a Biased S1PR Ligand, Increases Mitochondrial Function through STAT3 Activation in Cardiac Cells.

ABSTRACT: FTY720 is an FDA-approved sphingosine derivative drug for the treatment of multiple sclerosis. This compound blocks lymphocyte egress from lymphoid organs and autoimmunity through sphingosine 1-phosphate (S1P) receptor blockage. Drug repurposing of FTY720 has revealed improvements in glucose metabolism and metabolic diseases. Studies also demonstrate that preconditioning with this compound preserves the ATP levels during cardiac ischemia in rats. The molecular mechanisms by which FTY720 promotes metabolism are not well understood. Here, we demonstrate that nanomolar concentrations of the phosphorylated form of FTY720 (FTY720-P), the active ligand of S1P receptor (S1PR), activates mitochondrial respiration and the mitochondrial ATP production rate in AC16 human cardiomyocyte cells. Addition

SUBMITTER: Munoz JP 

PROVIDER: S-EPMC10139230 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature