Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation
| العنوان: | Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation |
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| المؤلفون: | Regina P. Markus, Cathy Vaillancourt, Lucas Sagrillo-Fagundes, Eugania Maria Assuncao Salustiano, Rodrigo Ruano |
| المساهمون: | Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Mayo Clinic [Rochester], University of São Paulo (USP), upported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) (no. 262011‐2009) to CV as well as by fellowship to EMAS from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and from the Programme de bourses d'excellence pour étudiants étrangers du Ministère de l’Éducation, de l'Enseignement superieurs et de la recherche (MEESR)‐Fonds de recherché du Québec‐Nature et technologies (FRQNT), by studentship awards to LSF from the Ministère de l’Éducation, du loisir et du sport (MELS), du Québec‐Fonds de recherché du Québec‐Nature e technologies (FRQNT) and also studentship from Fondation Armand Frappier, and from Fondation Armand Frappier and Réseau Québécois en reproduction (RQR)‐NSERC‐Collaborative Research., The authors thank women who donated their placentas for this study. We would like to thank Laetitia Laurent, Ph.D., for her technical support in the laboratory |
| المصدر: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Journal of Pineal Research Journal of Pineal Research, Wiley, 2018, 65 (4), pp.e12520. ⟨10.1111/jpi.12520⟩ |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, MESH: Melatonin/metabolism, [SDV]Life Sciences [q-bio], Placenta, syncytiotrophoblast, TNF, Fluorescent Antibody Technique, Chorionic Gonadotropin, MESH: Pregnancy, Endocrinology, interleukin (IL)-6, Pregnancy, PLACENTA, Phosphorylation, MESH: Fluorescent Antibody Technique, Cells, Cultured, Melatonin, MESH: Immunoblotting, Chemistry, NF-kappa B, MESH: Trophoblasts/metabolism, Cell Hypoxia, Interleukin-10, Trophoblasts, medicine.anatomical_structure, IL-10, embryonic structures, Female, Tumor necrosis factor alpha, MESH: NF-kappa B/metabolism, medicine.symptom, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured, medicine.drug, medicine.medical_specialty, MESH: Inflammation/metabolism, Immunoblotting, Inflammation, arylalkylamine N-acetyltransferase (AANAT), villous cytotrophoblasts, 03 medical and health sciences, MESH: Chorionic Gonadotropin/metabolism, Syncytiotrophoblast, Internal medicine, Autophagy, medicine, Humans, MESH: Interleukin-10/metabolism, MESH: Humans, MESH: Phosphorylation, L-Lactate Dehydrogenase, Interleukin-6, MESH: Interleukin-6/metabolism, MESH: Autophagy/physiology, Trophoblast, MESH: Cell Hypoxia/physiology, MESH: Placenta/cytology, 030104 developmental biology, MESH: L-Lactate Dehydrogenase/metabolism, Apoptosis, MESH: Female, NFκB |
| الوصف: | International audience; Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R-induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O2 ), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O2 , for 4 hour) or normoxia. H/R decreased endogenous melatonin synthesis (by 68%) and interleukin (IL)-10 levels (by 72%), coupled to increased tumor necrosis factor (TNF) (by 114%), IL-6 (by 55%), and NFκB (by 399%), compared to normoxia. Melatonin treatment reversed the H/R effect, restoring IL-10, TNF, and IL-6 levels to those of the normoxia condition. Melatonin, as well as NFκB inhibition, enhanced autophagy activation, consequently increasing syncytiotrophoblast survival in H/R conditions. This study suggests that H/R, which is present in pregnancy complications, inhibits endogenous melatonin production, thereby contributing to reduced syncytiotrophoblast viability. Results indicate that exogenous melatonin treatment may afford protection against H/R-induced damage, thereby enhancing placental cell survival, and contributing to improved fetal outcomes. |
| تدمد: | 0742-3098 1600-079X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e49823b5b33758abba1805f9d241d97f https://doi.org/10.1111/jpi.12520 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e49823b5b33758abba1805f9d241d97f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 07423098 1600079X |
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