دورية أكاديمية
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Melatonin regulates the antioxidant capacity of sheep granulosa cells through a novel uORF-Nrf2aa mediated Nrf2/KEAP1 pathway.

التفاصيل البيبلوغرافية
العنوان: Melatonin regulates the antioxidant capacity of sheep granulosa cells through a novel uORF-Nrf2aa mediated Nrf2/KEAP1 pathway.
المؤلفون: Ma J; Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China., Liu L; Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China., Yang H; Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China., Wan Y; Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China., Zhang Y; Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China., Wang F; Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, China. Electronic address: caeet@njau.edu.cn.
المصدر: Life sciences [Life Sci] 2024 Jul 15; Vol. 349, pp. 122693. Date of Electronic Publication: 2024 May 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
مواضيع طبية MeSH: Melatonin*/pharmacology , Melatonin*/metabolism , Granulosa Cells*/metabolism , Granulosa Cells*/drug effects , NF-E2-Related Factor 2*/metabolism , Kelch-Like ECH-Associated Protein 1*/metabolism , Antioxidants*/pharmacology , Antioxidants*/metabolism , Oxidative Stress*/drug effects , Signal Transduction*/drug effects , Open Reading Frames*, Animals ; Female ; Sheep ; Reactive Oxygen Species/metabolism ; Apoptosis/drug effects ; Cells, Cultured
مستخلص: Ovarian dysfunction stands as a prevalent contributor to female infertility, with its etiology intertwined with genetic, autoimmune, and environmental factors. Within the ovarian follicles, granulosa cells (GCs) represent the predominant cell population. Alterations in GCs, notably oxidative stress (OS) and the consequential surge in reactive oxygen species (ROS), play pivotal roles in the orchestration of ovarian function. Nrf2aa, a newly identified upstream open reading frame (uORF), is situated within the 5' untranslated region (5'UTR) of sheep Nrf2 mRNA and is regulated by melatonin, a crucial intrafollicular antioxidant. In this study, we have noted that Nrf2aa has the capacity to encode a peptide and exerts a negative regulatory effect on the translation efficiency (TE) of the Nrf2 CDs region. Further in vitro experiments, we observed that interfering with Nrf2aa can enhance the cellular functionality of GCs under 3-np-induced oxidative stress, while overexpressing Nrf2aa has the opposite effect. Furthermore, overexpression of Nrf2aa counteracts the rescuing effect of melatonin on the cellular functions of GCs under oxidative stress conditions, including estrogen secretion, proliferation, apoptosis, and many more. Finally, we confirmed that Nrf2aa, by regulating the expression of key proteins in the Nrf2/KEAP1 signaling pathway, further modulates the antioxidant levels in GCs.
Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Granulosa cells; Melatonin; Nrf2aa; Oxidative stress; uORF
المشرفين على المادة: JL5DK93RCL (Melatonin)
0 (NF-E2-Related Factor 2)
0 (Kelch-Like ECH-Associated Protein 1)
0 (Antioxidants)
0 (Reactive Oxygen Species)
تواريخ الأحداث: Date Created: 20240506 Date Completed: 20240601 Latest Revision: 20240610
رمز التحديث: 20240610
DOI: 10.1016/j.lfs.2024.122693
PMID: 38710277
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0631
DOI:10.1016/j.lfs.2024.122693