In Vivo Molecular Modulation of P-AKT, XIAP, and COX-2 Pathways, and Cellular Proliferation by Resveratrol in Uteri of Immature Rats.
Notice bibliographique
Résumé
Resveratrol (trans-3,4N-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with anticancer properties. Anticancerous properties of this antioxidant are exerted by antiproliferative and pro-apoptotic activities in various cancer cell types, but its molecular effect on uterine cells, both in normal and cancerous cells, is poorly understood. We have reported previously, that resveratrol can modulate COX-2 and AKT expressions/activities in endometrial cancer cells, and thus reverse cellular resistance associated with overexpression of these proteins. It has been reported that postnatal exposure to resveratrol may affect estrogenic activity in specific peripheral tissues (e.g. gonads), and differ from most other phytoestrogens by acting as a possible mixed ER agonist/antogonist, depending on the tissu-specific availability of ER subtypes. The aim of the present study was to investigate in vivo, in normal endometrial cells, if resveratrols protective effect would also involve COX-2 and AKT pathways, and/or ER. Healthy immature Sprague-Dowley rats were treated s.c. with resveratrol (0, 0.5, 5, 50 mg/kg/day) for 7 consecutive days, and sacrificed on the 8th day. Uteri were collected, weighted and endometrium was recovered for total protein extraction. Western blot analysis of protein expression were conducted and quantified. ER-alpha and beta affinity and activation by resveratrol were also determined by in vitro ER-binding and ERE-Luciferase activation assays. The results showed that 5.0 mg/kg body weight of resveratrol s.c. could increase uterine wet weight and uterine-body weight ratios significantly (P<0.05). This local cellular proliferation was accompanied by an increase of AKT phosphorylation and an increase of COX-2 and XIAP protein expression. AKT and ERs protein expression were not modulated by the treatment. Resveratrol showed moderate estrogenicity for both ER isoforms, low binding-affinity/activation, favouring ER-beta. In normal rats in vivo, resveratrol triggers phosphorylation of AKT and the downstream cascade involving XIAP and COX-2, stimulating proliferation of the epithelium and the glandular environment. Thus, thickening the columnar epithelial cells or an increase in the number of glands in endometrium of mature females could positively affect the outcome of pregnancy and favour fertility. These data support the hypothesis that resveratrol can act in a pro-survival or pro-apototic way, through AKT/p-AKT, XIAP and COX-2 regulation, depending on the localisation and the nature of the cells involved. Supported by NSERC (238501-06).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».