Caffeic acid phenethyl ester accumulates beta-catenin through GSK-3beta and participates in proliferation through mTOR in C2C12 cells.
OBJECTIVE
The aim of this study is to characterize the roles of caffeic acid phenethyl ester (CAPE) in the skeletal muscle cells.


METHODS
We performed immunoblotting assay using various phosphorylation specific antibodies.


RESULTS
We found that CAPE induces rapid and transient phosphorylation of glycogen synthase kinase (GSK)-3beta in a phosphoinositide 3-kinase (PI3K)-dependent manner. CAPE also decreases phosphorylation of beta-catenin, ultimately leading to beta-catenin accumulation. In addition, we demonstrated that CAPE activated the mammalian target of rapamycin (mTOR)-p70 S6 ribosomal kinase (S6K) and also stimulated extracellular signal-regulated kinase (ERK). The inhibition of mTOR blocked CAPE-induced ERK phosphorylation.


CONCLUSIONS
Our results suggest that CAPE may act through beta-catenin accumulation via stimulation of GSK-3beta and may also participate in cellular proliferation through the mTOR-ERK pathway.
Lee
Eun Soo
ES
Department of Anatomy, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
Lee
Jung-Ok
JO
Lee
Soo Kyung
SK
Kim
Ji Hae
JH
Jung
Jin Hee
JH
Keum
Bora
B
Park
Sun-Hwa
SH
Kim
Hyeon Soo
HS
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002109:Caffeic Acids / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D007202:Indicators and Reagents; D051379:Mice; D032446:Myoblasts / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D051176:beta Catenin / Q000378:metabolism*
D000199:Actins; D002109:Caffeic Acids; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007202:Indicators and Reagents; D010626:Phenylethyl Alcohol; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051176:beta Catenin; C546843:mTOR protein, mouse; C000605507:Gsk3b protein, mouse; C055494:caffeic acid phenethyl ester