Sevoflurane inhibits the self-renewal of mouse embryonic stem cells via the GABAAR-ERK signaling pathway
| Autor: | Yali Ge, Ju Gao, Loujing Zhou, Liuqing Yang, Shunyan Lin, Xiangzhi Fang |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Methyl Ethers Cancer Research animal structures Biology Biochemistry Sevoflurane 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation 030202 anesthesiology Genetics medicine Animals Cell Self Renewal RNA Small Interfering Extracellular Signal-Regulated MAP Kinases Molecular Biology Oncogene Mouse Embryonic Stem Cells Receptors GABA-A Embryonic stem cell Cell biology 030104 developmental biology Oncology Apoptosis Gene Knockdown Techniques Immunology Anesthetic Anesthetics Inhalation Molecular Medicine Signal transduction medicine.drug Signal Transduction |
| Zdroj: | Molecular medicine reports. 14(3) |
| ISSN: | 1791-3004 |
| Popis: | A large number of pregnant women are exposed to inhalation anesthetics for non‑obstetric surgery. Previous studies have demonstrated the toxicity to the developing fetus caused by the inhalation anesthetic sevoflurane, which can permeate rapidly through the placental barrier. However, the mechanism of embryotoxicity remains largely unknown. The present study used mouse embryonic stem cells (mES cells) as an early development model, in order to investigate the mechanism underlying the embryo toxicity of sevoflurane and found that sevoflurane inhibited the self‑renewal of mES cells. Sevoflurane was shown to upregulate the level of phosphorylated extracellular signal‑regulated kinase (p‑ERK) but it did not affect the total expression of ERK by γ-aminobutyric acid A receptor (GABAAR). Knockdown of the GABAAR rescued the upregulation of p‑ERK and inhibition of self‑renewal induced by sevoflurane in mES cells. Additionally, inhibition of the activity of ERK signaling can rescue the influence of sevoflurane on mES cells. In conclusion, sevoflurane inhibited the self‑renewal of mES cells by GABAAR/ERK signaling, which may be a potential therapeutic target to prevent the embryotoxicity of sevoflurane. |
| Databáze: | OpenAIRE |
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