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Molecular mechanisms of regulation of melatonin synthesis in pineal gland

松果体褪黑激素合成调节的分子机制

基本信息

批准号：
12470500
负责人：
MORIYAMA Yoshinori
金额：
$ 3.07万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

Pineal gland converts time signals from SCN to hormonal signals : pinealocytes synthesize melatonin as a circadyan rhythm hormone, and secrete it through blood stream. Serotonin N-acetyltransferase (SNAT) plays a sentral role for synthesis of melatonin, and thus, its activities are definitly controlled through several pathways. In the research project, we found two distinct novel regulatory mechanisms for SNAT regulation : [I] L-glutamate-mediated autonomic regulation, and [II] intramolecular regulation through cleavage of disulfide bond. The summary of each systems are as follows :[I] Overall characteristics of the L-glutamate-mediated autonomic regulatory system. We found that pinealocytes are glutamatergic. The cells store L-glutamate in synaptic-like microvesicles and secrete it through exocytosis. The released glutamate is involved in negative regulation of melatonin synthesis. We have identified and characterized various receptors and transporters involving in the processes. We have solved the molecular mechanism of L-glutamate secretion.[II] The mechanism of intramolecular regulation of SNAT. We found that SNAT showed two forms (active and inactive state) through exchange of -S-S- to -SH and HS-. We identified two systein residues incolving the processes. We found that this regulation also occurs under physiological conditions, and play a central role in SNAT regulation.

松果体将SCN的时间信号转化为激素信号：松果体细胞合成褪黑激素作为昼夜节律激素，并通过血液分泌。血清素n -乙酰转移酶（SNAT）在褪黑激素的合成中起着核心作用，因此，它的活性肯定是通过几种途径控制的。在本研究项目中，我们发现了两种不同的SNAT调控机制：[I] l -谷氨酸介导的自主调控，[II]通过二硫键裂解的分子内调控。各系统综述如下：[1]l -谷氨酸介导的自主调节系统的总体特征。我们发现松果体细胞具有谷氨酸能。细胞将l -谷氨酸储存在突触样微泡中，并通过胞吐分泌。释放的谷氨酸参与褪黑激素合成的负调控。我们已经确定并表征了参与这一过程的各种受体和转运体。我们已经解决了l -谷氨酸分泌的分子机制。[II] SNAT的分子内调控机制。我们发现SNAT通过- s - s -与- sh和HS-的交换表现出活性和非活性两种形态。我们确定了两个涉及该过程的系统残基。我们发现这种调控也发生在生理条件下，并在SNAT调控中发挥核心作用。