Centro de Investigaciones Endocrinológicas, "Dr César Bergadá," CONICET-FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
J Cell Biochem. 2018 Dec;119(12):10131-10142. doi: 10.1002/jcb.27350. Epub 2018 Aug 20.
Resveratrol (RSV), a polyphenolic compound largely found in red grape skin, has been used as a nutritional supplement as it exhibits beneficial health effects, such as anticancer, cardioprotective, antiaging, and anti-inflammatory. Particularly, it has been shown that it participates in the mechanisms involved in cell proliferation. Sirtuin 1 (SIRT1) is considered a well-known RSV effector. Noteworthy, Sirt1-knockout animals are infertile. The aim of this study was, first, to determine whether RSV has any effect on Sertoli cell proliferation and, second, whether SIRT1, a putative target of RSV, is present in immature Sertoli cells. Sertoli cell cultures obtained from 8-day-old rats, which actively proliferate, were treated with RSV (10 and 50 µM) under basal and follicle-stimulating hormone (FSH)-stimulated conditions. Bromodeoxyuridine (BrdU) incorporation and the expression of cyclins D1, D2, D3, E1, and E2 and the Cip/Kip cell cycle inhibitors p21 and p27 were analyzed. RSV decreased BrdU incorporation and cyclins D1, D2, E1, and E2 expression and increased p21 and p27 messenger RNA (mRNA) levels. RSV also decreased FSH-stimulated BrdU incorporation and cyclins D1 and D2 mRNA levels. The effect of RSV on cMYC was also analyzed. RSV treatment did not modify basal and FSH-stimulated cMyc expression; however, it inhibited basal and FSH-stimulated cMYC transcriptional activity, suggesting a role of cMYC in RSV effects. Additionally, Sirt1 was detected in immature Sertoli cells. Altogether, these results suggest that RSV possibly, by activating SIRT1 and regulating cMYC transcriptional activity, participates in the regulation of immature Sertoli cell proliferation.
白藜芦醇（RSV）是一种主要存在于红葡萄皮中的多酚化合物，已被用作营养补充剂，因为它具有有益的健康作用，如抗癌、心脏保护、抗衰老和抗炎。特别是，已经表明它参与了细胞增殖的机制。Sirtuin 1（SIRT1）被认为是 RSV 的一种有效因子。值得注意的是，Sirt1 敲除动物是不育的。本研究的目的首先是确定 RSV 是否对支持细胞增殖有任何影响，其次是确定 Sirt1 是否存在于未成熟的支持细胞中，Sirt1 是 RSV 的一个假定靶点。从 8 天大的大鼠中获得的支持细胞培养物，它们处于活跃的增殖状态，在基础条件和卵泡刺激素（FSH）刺激条件下用 RSV（10 和 50μM）处理。用溴脱氧尿苷（BrdU）掺入和细胞周期蛋白 D1、D2、D3、E1 和 E2 的表达以及细胞周期抑制剂 p21 和 p27 的 Cip/Kip 进行分析。RSV 降低了 BrdU 掺入和细胞周期蛋白 D1、D2、E1 和 E2 的表达，并增加了 p21 和 p27 的信使 RNA（mRNA）水平。RSV 还降低了 FSH 刺激的 BrdU 掺入和细胞周期蛋白 D1 和 D2 的 mRNA 水平。还分析了 RSV 对 cMYC 的影响。RSV 处理并没有改变基础和 FSH 刺激的 cMyc 表达；然而，它抑制了基础和 FSH 刺激的 cMYC 转录活性，这表明 cMYC 在 RSV 作用中起作用。此外，在未成熟的支持细胞中检测到 Sirt1。总的来说，这些结果表明 RSV 可能通过激活 SIRT1 和调节 cMYC 转录活性，参与调节未成熟支持细胞的增殖。
