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- Title
Linoleic Acid Induces Mouse Embryonic Stem Cell Proliferation Via Ca/PKC, PI3K/Akt, and MAPKs.
- Authors
Min Hee Kim; Mi Ok Kim; Yun Hee Kim; Jin Sang Kim; Ho Jae Han
- Abstract
Aims: This study investigated the effect of linoleic acid (LA) on cell proliferation and the related signaling cascade in mouse embryonic stem (ES) cells. Materials & 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- (≥ 10-9 M) and time- (≥ 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). Conclusion: LA stimulated cell proliferation via Ca2 , PLC/PKC, PI3K/Akt, and p44/42 MAPKs signaling pathways in mouse ES cells. Copyright © 2009 S. Karger AG, Basel
- Subjects
FATTY acids; LINOLEIC acid; ORGANELLES; CELL membranes; MOLECULES; GENE expression
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2009, Vol 23, Issue 1-3, p053
- ISSN
1015-8987
- Publication type
Academic Journal
- DOI
10.1159/000204090