Trichostatin A reduces GnRH mRNA expression with a concomitant increase in retinaldehyde dehydrogenase in GnRH-producing neurons
Trichostatin A reduces GnRH mRNA expression with a concomitant increase in retinaldehyde dehydrogenase in GnRH-producing neurons
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DOI：
10.1016/j.mce.2015.06.017
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发表时间：
2015-09
影响因子：
4.1
通讯作者：
H. Kanasaki;T. Mijiddorj;Unurjargal Sukhbaatar;A. Oride;Tomoko Ishihara;Ikuko Yamagami;S. Kyo
中科院分区：
文献类型：
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作者：
H. Kanasaki;T. Mijiddorj;Unurjargal Sukhbaatar;A. Oride;Tomoko Ishihara;Ikuko Yamagami;S. Kyo
Trichostatin A (TSA) 是哺乳动物组蛋白脱乙酰酶的选择性抑制剂，广泛用于通过干扰组蛋白脱乙酰化来改变 DNA 转录因子在染色质内结合 DNA 的能力。在产生 GnRH 的神经元细胞系 GT1-7 中，TSA 显着降低了 GnRH mRNA 的表达。 Kisspeptin 是一种已知的 GnRH 释放调节剂，它不能增加 GnRH mRNA 表达，也不能改变 TSA 诱导的 GnRH 表达减少。 TSA（而非 Kisspeptin）增加全细胞裂解物中的组蛋白乙酰化，并显着刺激视黄醛脱氢酶 (RALDH) 的表达，RALDH 是一种已知参与细胞分化的视黄酸 (RA) 合成酶。此外，用RA处理GT1-7细胞可剂量依赖性地抑制GnRH mRNA的表达。然而，TSA 诱导的 GnRH mRNA 减少不受泛 RA 受体反向激动剂 BMS493 或 RA 代谢抑制剂利拉唑治疗的调节。我们目前的结果表明，RALDH 和 RA 可能不直接参与 TSA 诱导的 GnRH 表达减少，但这些物质可能是 GnRH 的新型调节剂。
Trichostatin A (TSA) is a selective inhibitor of mammalian histone deacetylase and is widely used to modify the ability of DNA transcription factors to bind DNA within chromatin by interfering with histone deacetylation. In the GnRH-producing neuronal cell line GT1-7, TSA significantly reduced expression of GnRH mRNA. Kisspeptin, a known regulator of GnRH release, failed to increase GnRH mRNA expression and did not modify TSA-induced reduction of GnRH expression. TSA, but not kisspeptin, increased histone acetylation in whole-cell lysates and significantly stimulated the expression of retinaldehyde dehydrogenase (RALDH), a retinoic acid (RA)-synthesizing enzyme that is known to be involved in cell differentiation. In addition, treatment of the GT1-7 cells with RA dose-dependently inhibited the expression of GnRH mRNA. Whereas, TSA-induced reduction of GnRH mRNA was not modulated by treatment with the pan-RA receptor inverse agonist BMS493 or the RA metabolism inhibitor liarozole.Our current results suggest that the RALDH and RA might not be directly involved in the reduction of GnRH expression induced by TSA, however these substances could be a novel regulator of GnRH.