Lithium Chloride Increases COX-2 Expression and PGE2 Production in a Human Granulosa-Lutein SVOG Cell Line Via a GSK-3β/β-Catenin Signaling Pathway
| Autor: | Guiyan Chu, Long Bai, Peter C.K. Leung, Hsun-Ming Chang, Jung-Chien Cheng, Gongshe Yang |
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| Rok vydání: | 2017 |
| Předmět: |
inorganic chemicals
0301 basic medicine medicine.medical_specialty Beta-catenin Dinoprostone Cell Line 03 medical and health sciences Endocrinology Downregulation and upregulation Luteal Cells Internal medicine medicine Humans Glycogen synthase GSK3B Protein kinase B beta Catenin Glycogen Synthase Kinase 3 beta biology Chemistry Kinase Up-Regulation Cell biology 030104 developmental biology Cyclooxygenase 2 biology.protein Phosphorylation Female Signal transduction Lithium Chloride Signal Transduction |
| Zdroj: | Endocrinology. 158:2813-2825 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Lithium chloride (LiCl) is widely prescribed for the treatment of bipolar disorders and is associated with a higher incidence of reproductive adverse effects. Cyclooxygenase (COX)-2 and its derivative, prostaglandin E2 (PGE2), play regulatory roles in the human ovulatory process. Whether LiCl affects ovulation by regulating COX2 expression and PGE2 production in the human ovary is still largely unknown. The aim of this study was to investigate the effect of LiCl on the expression of COX-2 and production of PGE2 in human granulosa-lutein (hGL) cells, as well as the mechanisms underlying this effect. Both immortalized and primary hGL cells were used as research models. Using dual inhibition approaches, our results show that LiCl initiates the hGL cellular action by inhibiting the activity of glycogen synthase kinase-3β [GSK-3β (phosphorylation of GSK-3β)] and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not by affecting protein kinase B or cAMP response element binding protein signaling. Additionally, the phosphorylation of GSK-3β, but not ERK1/2, resulted in the stabilization and nuclear localization of β-catenin. Furthermore, knockdown of either β-catenin or GSK-3β reversed the LiCl-induced upregulation of COX-2 expression. These results indicate that LiCl upregulates the expression of COX-2 and the subsequent production of PGE2 through the canonical GSK-3β/β-catenin signaling pathway in hGL cells. |
| Databáze: | OpenAIRE |
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