Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (Bim(EL)) in Porcine Granulosa Cells.
Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (Bim(EL)) in Porcine Granulosa Cells.
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褪黑素促进猪颗粒细胞中磷酸化促凋亡蛋白 Bcl-2 相互作用介导的细胞死亡超长 (BimEL) 的泛素化
DOI：
10.3390/ijms19113431
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发表时间：
2018-11-01
影响因子：
5.6
通讯作者：
Zeng S
中科院分区：
文献类型：
--
作者：
Wang Y;Zeng S
褪黑素(N-乙酰-5-甲氧基色胺)存在于卵泡液中，其浓度与卵泡的健康状况密切相关。然而，褪黑素在卵泡中作用的分子机制尚不确定。本研究测定了健康不同阶段猪卵泡液中褪黑激素的浓度。随着卵泡闭锁，褪黑素浓度下降，提示褪黑素可能参与了卵泡健康的维持。进一步研究了褪黑素调节卵泡发育的分子途径。促凋亡蛋白BimEL是卵泡闭锁过程中控制颗粒细胞凋亡的关键蛋白，被选为靶分子。猪颗粒细胞在含有10−、9M褪黑素和卵丘卵母细胞复合体或卵泡刺激素的培养液中，BimEL表达下调。有趣的是，ERK介导的磷酸化是褪黑素诱导BimEL下降的先决条件，褪黑素只促进磷酸化的BimEL的泛素化，而不影响溶酶体或蛋白酶体的活性。此外，褪黑素诱导的BimEL下调不依赖于其受体和抗氧化特性。综上所述，褪黑素可能通过诱导BimEL泛素化抑制颗粒细胞的凋亡来维持卵泡的健康。
Melatonin (N-acetyl-5-methoxytryptamine) is found in ovarian follicular fluid, and its concentration is closely related to follicular health status. Nevertheless, the molecular mechanisms underlying melatonin function in follicles are uncertain. In this study, melatonin concentration was measured in porcine follicular fluid at different stages of health. The melatonin concentration decreased as the follicles underwent atresia, suggesting that melatonin may participate in the maintenance of follicular health. The molecular pathway through which melatonin may regulate follicular development was further investigated. The pro-apoptotic protein BimEL (Bcl-2-interacting mediator of cell death-Extra Long), a key protein controlling granulosa cell apoptosis during follicular atresia, was selected as the target molecule. BimEL was downregulated when porcine granulosa cells were cultured in medium containing 10−9 M melatonin and isolated cumulus oocyte complexes (COCs) or follicle stimulating hormone (FSH). Interestingly, ERK-mediated phosphorylation was a prerequisite for the melatonin-induced decline in BimEL, and melatonin only promoted the ubiquitination of phosphorylated BimEL, and did not affect the activities of the lysosome or the proteasome. Moreover, the melatonin-induced downregulation of BimEL was independent of its receptor and its antioxidant properties. In conclusion, melatonin may maintain follicular health by inducing BimEL ubiquitination to inhibit the apoptosis of granulosa cells.
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影响因子：
16
作者：
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通讯作者：
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影响因子：
2.5
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作者：
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通讯作者：
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影响因子：
4.8
作者：
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