Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary.
Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary.
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白藜芦醇促进大鼠卵巢颗粒细胞中SIRT1和Star的表达：SIRT1在卵巢中的隐含作用。
DOI：
10.1186/1477-7827-10-14
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发表时间：
2012-02-23
期刊：
影响因子：
--
通讯作者：
Taketani Y
中科院分区：
文献类型：
--
作者：
Morita Y;Wada-Hiraike O;Yano T;Shirane A;Hirano M;Hiraike H;Koyama S;Oishi H;Yoshino O;Miyamoto Y;Sone K;Oda K;Nakagawa S;Tsutsui K;Taketani Y
白藜芦醇是一种天然多酚化合物，以其对能量稳态的有益作用而闻名，它还具有多种特性，包括抗氧化，抗炎和抗肿瘤活性。最近，沉默信息调节基因（Sirtuins）已被确定为白藜芦醇的靶点。Sirtuin 1（SIRT 1）最初被发现为NAD+依赖性组蛋白脱乙酰酶，是热量限制下游途径的主要调节剂，并且SIRT 1的活化改善葡萄糖稳态和胰岛素敏感性。迄今为止，SIRT 1在卵巢中的存在和生理作用尚不清楚。在这里，我们发现SIRT 1定位于人类卵巢的颗粒细胞。分析了白藜芦醇和SIRT 1在卵巢中的生理作用。免疫组化定位SIRT 1的表达。Western blot检测体外培养细胞及黄体化颗粒细胞SIRT 1蛋白表达。大鼠颗粒细胞获自己烯雌酚处理的大鼠。细胞用增加剂量的白藜芦醇处理，随后收获以确定mRNA水平和蛋白质水平。通过MTS测定法测试细胞活力。Caspase 3/7活性检测和Hoechst 33342染色检测细胞凋亡。SIRT 1蛋白在人卵巢组织和人黄素化颗粒细胞中均有表达。我们证明了白藜芦醇对大鼠颗粒细胞的活力表现出有效的浓度依赖性抑制作用。然而，白藜芦醇诱导的大鼠颗粒细胞活力的抑制是独立的凋亡信号。白藜芦醇增加SIRT 1，LH受体，星星和P450芳香化酶的mRNA水平，而FSH受体的mRNA水平保持不变。Western blot分析结果与实时荧光定量RT-PCR检测结果一致。此外，孕酮分泌诱导白藜芦醇的治疗。这些结果提示了白藜芦醇促进卵巢孕酮分泌和促黄体化相关基因表达的新机制，从而为了解黄体功能不全的发病机制提供了重要启示。
Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary. The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining. SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol. These results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency.
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影响因子：
4.4
作者：
Manna, SK;Mukhopadhyay, A;Aggarwal, BB
通讯作者：
Aggarwal, BB
DOI：
10.1073/pnas.94.25.14138
发表时间：
1997-12-09
影响因子：
11.1
作者：
Gehm, BD;McAndrews, JM;Jameson, JL
通讯作者：
Jameson, JL
影响因子：
4.8
作者：
Chen, QM;Yano, T;Taketani, Y
通讯作者：
Taketani, Y
影响因子：
3.9
作者：
Chung, Sangwoon;Yao, Hongwei;Caito, Samuel;Hwang, Jae-Woong;Arunachalam, Gnanapragasam;Rahman, Irfan
通讯作者：
Rahman, Irfan
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.