title: Cis-9,trans-11-conjugated linoleic acid promotes neuronal differentiation through regulation of Hes6 mRNA and cell cycle in cultured neural stem cells.
abstract: Conjugated linoleic acids (CLAs) are positional and geometrical isomers of linoleic acid (LA). Cis-9,trans-11-CLA (CLA), the main isomer of CLAs in foods derived from ruminants, has several beneficial effects for humans and animals; however, its effects on the central nervous system are largely unknown. In this study, we investigated the effects of LA and CLA on neuronal differentiation of neural stem cells (NSCs). NSCs cultured with or without LA and CLA were assessed by immunofluorescence staining, mRNA measurement of basic helix-loop-helix transcription factors and cyclin-dependent kinase inhibitors by real-time PCR, BrdU incorporation analysis and flow cytometry analysis. In NSCs treated with CLA, the number of Tuj-1-positive cells (neurons) and the mRNA expression levels of Hes6, MAP2, p21(cip1) and p27(kip1) increased, while the proportion of S-phase cells decreased; compared with the control, no change was demonstrated in NSCs treated with LA. These results suggest that CLA promotes neuronal differentiation by increasing, in part, the expression of Hes6 mRNA and by activating p21(cip1) and p27(kip1) to arrest cell cycle.
authors: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors: Toshiyuki
authors: T
authors: Okui
authors: Michio
authors: M
authors: Hashimoto
authors: Masanori
authors: M
authors: Katakura
authors: Osamu
authors: O
authors: Shido
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D019787:Linoleic Acid / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019787:Linoleic Acid; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; C493962:Cdkn1b protein, rat; C568822:Hes6 protein, rat; C503589:cis-9, trans-11-conjugated linoleic acid