Linoleic acid induces mouse embryonic stem cell proliferation via Ca2+/PKC, PI3K/Akt, and MAPKs.
OBJECTIVE
This study investigated the effect of linoleic acid (LA) on cell proliferation and the related signaling cascade in mouse embryonic stem (ES) cells.


METHODS
To examine effects of LA, mouse ES cells (ES-E14TG2a) were used. Moreover, DNA synthesis, glucose production, protein and mRNA expressions were measured.


RESULTS
LA increased DNA synthesis in a concentration- (> or = 10(-9) M) and time- (> or = 24 h) dependent manner, as determined by [3H] thymidine incorporation and increased cell number. LA increased intracellular Ca2+ levels via regulation of phospholipase C (PLC) and activated protein kinase C (PKC). LA activated phosphatidylinositol 3-kinase (PI3K)/Akt and p44/42 mitogen-activated protein kinases (MAPKs). U73122 (PLC inhibitor), staurosporine (PKC inhibitor), LY294002 (PI3K inhibitor), and Akt inhibitor blocked the phosphorylation of p44/42 MAPKs. In addition, LA stimulated gluconeogenesis through increase expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). LA-induced increases in the cell cycle regulatory proteins, cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4, were blocked by U73122, staurosporine, LY294002, Akt inhibitor, PD98059, and metformin (gluconeogenesis inhibitor).


CONCLUSIONS
LA stimulated cell proliferation via Ca2+, PLC/PKC, PI3K/Akt, and p44/42 MAPKs signaling pathways in mouse ES cells.
Kim
Min Hee
MH
Department of Rehabilitation Science, Graduate School of Daegu University, Daegu, Korea.
Kim
Mi Ok
MO
Kim
Yun Hee
YH
Kim
Jin Sang
JS
Han
Ho Jae
HJ
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D019787:Linoleic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; D002118:Calcium