title: Effects of peroxisome proliferator-activated receptor alpha (PPARalpha) agonists on leucine-induced phosphorylation of translational targets in C2C12 cells.
abstract: Effect of peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, WY-14,643 (WY) and/or clofibrate, on the leucine-induced phosphorylation of translational targets in C2C12 myoblasts was studied. C2C12 cells were treated with WY or clofibrate for 24 h prior to stimulation with leucine. Western blot analyses revealed that the leucine-induced phosphorylation of p70 S6 kinase (p70S6K), a key regulator of translation initiation, was significantly higher in WY-treated cells than in control and clofibrate-treated cells. Phosphorylation of extracellular-regulated kinase (ERK1/2) was higher in WY-treated cells. WY treatment also increased the leucine-induced phosphorylation of ribosomal protein S6 and eukaryotic initiation factor 4B. In contrast, eukaryotic elongation factor 2, a marker for peptide chain elongation process, was significantly activated (dephosphorylated) only in leucine-stimulated control cells. Pre-treatment of the cells with PD98059 (ERK1/2 kinase inhibitor) prevented the phosphorylation of ERK1/2 and decreased the leucine-induced phosphorylation of p70S6K. It is concluded that WY increased the leucine-induced phosphorylation of target proteins involving in translation initiation via ERK/p70S6K pathway, but impaired the signaling for elongation process, suggesting that p70S6K phosphorylation may be essential, but not sufficient for the activation of entire targets for protein translation in WY-treated cells.
authors.affiliation: Department of Health and Sports Sciences, Graduate School of Medicine Bioscience, Osaka University, Osaka 560-0043, Japan. nakai@hss.osaka-u.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakai
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kawano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Terada
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Oke
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohira
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
mesh_terms: D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D002994:Clofibrate / Q000494:pharmacology*; D054736:Elongation Factor 2 Kinase / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D005419:Flavonoids; D009097:Multienzyme Complexes; D047493:PPAR alpha; D010750:Phosphoproteins; D011743:Pyrimidines; D038601:Ribosomal Protein S6; C031799:eIF-4B; C006253:pirinixic acid; C106281:Mknk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C517690:Eef2k protein, mouse; D054736:Elongation Factor 2 Kinase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D007930:Leucine; D002994:Clofibrate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus