Involvement of the ERK1/2 Pathway During Oxytocin-Induced PGF2alpha Production in the Bovine Endometrial Epithelial Cell Line bEEL.
Bibliographic record
Abstract
In ruminants, oxytocin (OT) initiates the pulsatile release of progstaglandin F2α (PGF2α) from the endometrial epithelial cells through the G protein coupled oxytocin receptor (OTR) that is up-regulated during the luteolytic phase. It has been proposed that the embryonic signal interferon tau exerts its antiluteolytic effect by disrupting the OT signaling axis. In this respect, we have studied the signaling pathway of OT-induced PGF2α production in bovine endometrial epithelial cell line (bEEL) using kinase inhibitors. Uncoupling OTR with suramin (100μM) inhibited OT (500nM)-induced PGF2α release confirming mediation through G protein subunits. OT induces intracellular Ca2+ mobilization suggesting Gαq/11 mediated signaling as was shown for myometrial OTRs. Surprisingly, however, neither the Ca2+ chelator BAPTA nor a PKC inhibitor had any effect on OT-induced PGF2α release. In contrast, the MEK inhibitor PD 98059 (10μM) and Raf1 inhibitor GW5074 (1μM) practically abolished OT-induced PGF2α production in bEEL cells, thus pointing at the involvement of the of ERK pathway. Inhibition of the small GTPase Ras by munanmyin (1μM) inhibited PGF2α by 50%; whereas LY 294002 (25μM) and AG1879 (10μM) inhibited OT-induced PGF2α production by 80-90% indicating the involvement of PI3K and Src, respectively. In addition, pertussis toxin (PTX 200 ngml-1) inhibited PGF2α production by 50% suggesting a role for Gαi/o; however, increasing intracellular cAMP by 8 bromo cAMP, forskolin or IBMX did not inhibit OT-induced PGF2α production suggesting involvement of Gαo rather than Gαi as the PTX sensitive subtype. Surprisingly, the inhibition of OT-induced PGF2α production was not accompanied by down regulation of COX2 expression. Therefore, phosphorylation of cPLA2, inhibition of COX2 activity, or uncoupling of PGF synthase from COX2 might be considered as alternate mechanisms behind the reduced PGF2α production. Our results suggest that OT-induced PGF2α production in bEEL cells is mediated principally through Gβ γ subunit initiating phosphorylation of downstream molecules such as PI3K, Src, Ras, Raf1, MEK and ERK kinases and co-regulated by PTX sensitive Gα. (poster)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".