PXR is a target of (-)-epicatechin in skeletal muscle
Miguel Ortiz-Flores,
Andrés Portilla-Martínez,
Francisco Cabrera-Pérez,
Nayelli Nájera,
Eduardo Meaney,
Francisco Villarreal,
Javier Pérez-Durán,
Guillermo Ceballos
Affiliations
Miguel Ortiz-Flores
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX, Mexico
Andrés Portilla-Martínez
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX, Mexico
Francisco Cabrera-Pérez
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX, Mexico
Nayelli Nájera
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX, Mexico
Eduardo Meaney
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX, Mexico
Francisco Villarreal
Medical School, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
Javier Pérez-Durán
Instituto Nacional de Perinatología, Calle Montes Urales 800, Lomas - Virreyes, Lomas de Chapultepec IV Secc, 11000 Ciudad de México, CDMX, Mexico
Guillermo Ceballos
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX, Mexico; Corresponding author.
(-)-Epicatechin (EC) is a flavanol that has shown numerous biological effects such as: decrease risk of cardiovascular dysfunction, metabolism regulation, skeletal muscle (SkM) performance improvement and SkM cells differentiation induction, among others. The described EC acceptor/receptor molecules do not explain the EC's effect on SkM. We hypothesize that the pregnane X receptor (PXR) can fulfill those characteristics, based on structural similitude between EC and steroidal backbone and that PXR activation leads to similar effects as those induced by EC. In order to demonstrate our hypothesis, we: 1) analyzed the possible EC and mouse PXR interaction through in silico strategies, 2) developed an EC's affinity column to isolate PXR, 3) evaluated, in mouse myoblast (C2C12 cells) the inhibition of EC-induced PXR's nucleus translocation by ketoconazole, a specific blocker of PXR and 4) analyzed the effect of EC as an activator of mouse PXR, evaluating the expression modulation of cytochrome 3a11 (Cyp3a11) gen and myogenin protein. (-)-Epicatechin interacts and activates PXR, promoting this protein translocation to the nucleus, increasing the expression of Cyp3a11, and promoting C2C12 cell differentiation through increasing myogenin expression. These results can be the base of further studies to analyze the possible participation of PXR in the skeletal muscle effects shown by EC.
