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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.
Pubmed ID: 28911173 RIS Download
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This monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (E10) Mouse mAb
View all literature mentionsThis monoclonal targets Non-phospho (Active) β-Catenin (Ser45) (D2U8Y) XP® Rabbit mAb recognizes endogenous levels of β-catenin protein only when Ser45 is not phosphorylated.
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis polyclonal targets COX2 / Cyclooxygenase 2 antibody
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis monoclonal targets CREB
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis monoclonal targets GSK-3 beta
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets CREB
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis polyclonal targets COX2 / Cyclooxygenase 2 antibody
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets CREB
View all literature mentionsThis monoclonal targets Non-phospho (Active) β-Catenin (Ser45) (D2U8Y) XP® Rabbit mAb recognizes endogenous levels of β-catenin protein only when Ser45 is not phosphorylated.
View all literature mentionsThis monoclonal targets GSK-3 beta
View all literature mentionsThis monoclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets GSK-3 beta
View all literature mentionsThis monoclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (E10) Mouse mAb
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets COX2 / Cyclooxygenase 2 antibody
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (E10) Mouse mAb
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Non-phospho (Active) β-Catenin (Ser45) (D2U8Y) XP® Rabbit mAb recognizes endogenous levels of β-catenin protein only when Ser45 is not phosphorylated.
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets COX2 / Cyclooxygenase 2 antibody
View all literature mentionsThis monoclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis monoclonal targets CREB
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis monoclonal targets Non-phospho (Active) β-Catenin (Ser45) (D2U8Y) XP® Rabbit mAb recognizes endogenous levels of β-catenin protein only when Ser45 is not phosphorylated.
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (E10) Mouse mAb
View all literature mentionsThis monoclonal targets GSK-3 beta
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
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