LIM homeobox transcription factor Isl1 is required for melatonin synthesis in the pig pineal gland
LIM homeobox transcription factor Isl1 is required for melatonin synthesis in the pig pineal gland
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LIM 同源框转录因子 Isl1 是猪松果体中褪黑激素合成所必需的。
DOI：
10.1111/jpi.12481
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发表时间：
2018-08
影响因子：
10.3
通讯作者：
Sheng Cui
中科院分区：
文献类型：
--
作者：
Jinglin Zhang;Jingtao Qiu;Yewen Zhou;Yue Wang;Hongjiao Li;Taojie Zhang;Ying Jiang;Kemian Gou;Sheng Cui
褪黑激素是调节昼夜节律、新陈代谢和生殖的关键激素。然而，褪黑激素的合成和分泌机制尚未完全确定。本研究旨在探讨LIM同源盒转录因子Isl 1在猪松果体褪黑素合成和分泌调控中的作用。我们发现Isl 1在猪松果体中的褪黑激素产生细胞中高度表达。进一步的功能研究表明，在培养的原代猪松果体细胞中，Isl 1敲低导致褪黑激素和芳基烷基胺N-乙酰转移酶（AANAT）mRNA水平分别下降29.2%和72.2%，而Isl 1过表达分别提高1.3倍和2.7倍。此外，去甲肾上腺素（NE）对褪黑激素合成的增强作用被Isl 1敲低所消除。在猪松果体中，脑室内NE注射使Isl 1 mRNA和蛋白水平上调约3倍和4.5倍。然后，我们研究了Isl 1表达的变化，在松果体和全球褪黑激素水平全天。结果表明，24：00时的Isl 1蛋白水平是12：00时的2.5倍，这与褪黑激素水平平行。我们进一步发现Isl 1增加AANAT启动子的活性，NE对Isl 1表达的影响被ERK抑制剂阻断。总的来说，这里提供的结果表明，Isl 1积极调节褪黑激素的合成，通过靶向AANAT，通过ERK信号通路的NE。这表明Isl 1在维持昼夜节律中起着重要作用。
Melatonin is a key hormone that regulates circadian rhythms, metabolism, and reproduction. However, the mechanisms of melatonin synthesis and secretion have not been fully defined. The purpose of this study was to investigate the functions of the LIM homeobox transcription factor Isl1 in regulating melatonin synthesis and secretion in porcine pineal gland. We found that Isl1 is highly expressed in the melatonin‐producing cells in the porcine pineal gland. Further functional studies demonstrate that Isl1 knockdown in cultured primary porcine pinealocytes results in the decline of melatonin and arylalkylamine N‐acetyltransferase (AANAT) mRNA levels by 29.2% and 72.2%, respectively, whereas Isl1 overexpression raised by 1.3‐fold and 2.7‐fold. In addition, the enhancing effect of norepinephrine (NE) on melatonin synthesis was abolished by Isl1 knockdown. The in vivo intracerebroventricular NE injections upregulate Isl1 mRNA and protein levels by about threefold and 4.5‐fold in the porcine pineal gland. We then examined the changes in Isl1 expression in the pineal gland and global melatonin levels throughout the day. The results show that Isl1 protein level at 24:00 is 2.5‐fold higher than that at 12:00, which is parallel to melatonin levels. We further found that Isl1 increases the activity of AANAT promoter, and the effect of NE on Isl1 expression was blocked by an ERK inhibitor. Collectively, the results presented here demonstrate that Isl1 positively modulates melatonin synthesis by targeting AANAT, via the ERK signaling pathway of NE. These suggest that Isl1 plays important roles in maintaining the daily circadian rhythm.
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影响因子：
3.1
作者：
Yamazaki F;Møller M;Fu C;Clokie SJ;Zykovich A;Coon SL;Klein DC;Rath MF
通讯作者：
Rath MF
影响因子：
5.8
作者：
T. Ogiwara;C. Chik;A. Ho
通讯作者：
T. Ogiwara;C. Chik;A. Ho
影响因子：
3.2
作者：
A. K-Laflamme;L. Wu;S. Foucart;J. de Champlain
通讯作者：
A. K-Laflamme;L. Wu;S. Foucart;J. de Champlain
DOI：
10.1016/s0169-328x(99)00175-8
发表时间：
1999-07
期刊：
Brain research. Molecular brain research
影响因子：
--
作者：
F. Gauer;V. Poirel;M. Garidou;V. Simonneaux;P. Pévet
通讯作者：
F. Gauer;V. Poirel;M. Garidou;V. Simonneaux;P. Pévet
影响因子：
4.6
作者：
V. Korzh;T. Edlund;S. Thor
通讯作者：
V. Korzh;T. Edlund;S. Thor