Acta pharmacologica Sinica, 2016-09, Vol.37 (9), p.1190-1198
2016
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- Autor(en) / Beteiligte
- Titel
- Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest
- Ist Teil von
- Acta pharmacologica Sinica, 2016-09, Vol.37 (9), p.1190-1198
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aim： Recent studies have shown that the two-pore-domain potassium channel TREK-1 is involved in the proliferation of neural stem cells, astrocytes and human osteoblasts. In this study, we investigated how TREK-1 affected the proliferation of Chinese hamster ovary （CHO） cells in vitro. Methods： A CHO cell line stably expressing hTREK-1 （CHO/hTREK-1 cells） was generated. TREK-1 channel currents in the cells were recorded using whole-cell voltage-clamp recording. The cell cycle distribution was assessed using flow cytometry analysis. The expression of major signaling proteins involved was detected with Western blotting. Results： CHO/hTREK-1 cells had a high level of TREK-1 expression, reached up to 320%±16% compared to the control cells. Application of arachidonic acid （10 μmol/L）, chloroform （1 mmol/L） or etomidate （10 μmol/L） substantially increased TREK-1 channel currents in CHO/hTREK-1 cells. Overexpression of TREK-1 caused CliO cells arresting at the G1 phase, and significantly decreased the expression of cyclin DI. The TREK-1 inhibitor/-butylphthalide （1-100 μmol/L） dose-dependently attenuated TREK-l-induced G1 phase cell arrest. Moreover, overexpression of TREK-1 significantly decreased the phosphorylation of Akt （S473）, glycogen synthase kinase-3β （S9） and cAMP response element-binding protein （CREB, S133）, enhanced the phosphorylation of p38 （T180/Y182）, but did not alter the phosphorylation and expression of signal transducer and activator of transcription 3 （STAT3）. Conclusion： TREK-1 overexpression suppresses CliO cell proliferation by inhibiting the activity of PKA and p38/MAPK signaling pathways and subsequently inducing G1 phase cell arrest.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1671-4083eISSN: 1745-7254DOI: 10.1038/aps.2016.65Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5022101
- Format
- –
- Schlagworte
- Animals, Arachidonic Acid - pharmacology, Benzofurans - pharmacology, Biomedical and Life Sciences, Biomedicine, Blotting, Western, Cell Proliferation - drug effects, Cell Proliferation - genetics, Chloroform - pharmacology, CHO Cells, Cricetinae, Cricetulus, Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors, Etomidate - pharmacology, Flow Cytometry, G1 Phase Cell Cycle Checkpoints - drug effects, G1 Phase Cell Cycle Checkpoints - genetics, Humans, Immunology, Internal Medicine, Medical Microbiology, Membrane Potentials - drug effects, Membrane Potentials - genetics, Original, original-article, p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors, Patch-Clamp Techniques, Pharmacology/Toxicology, Potassium Channels, Tandem Pore Domain - antagonists & inhibitors, Potassium Channels, Tandem Pore Domain - genetics, Signal Transduction, Transfection, Vaccine