Control of Polyamine Biosynthesis by Antizyme Inhibitor 1 Is Important for Transcriptional Regulation of Arginine Vasopressin in the Male Rat Hypothalamus.
Control of Polyamine Biosynthesis by Antizyme Inhibitor 1 Is Important for Transcriptional Regulation of Arginine Vasopressin in the Male Rat Hypothalamus.
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DOI：
10.1210/en.2015-1074
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发表时间：
2015-08
期刊：
影响因子：
4.8
通讯作者：
Murphy D
中科院分区：
文献类型：
--
作者：
Greenwood MP;Greenwood M;Paton JF;Murphy D
多胺、亚精胺和精胺是存在于所有活细胞中的小阳离子。在大脑中，这些阳离子在下丘脑的室旁核（PVN）和视上核（SON）的神经元中特别丰富，它们合成神经肽激素精氨酸加压素（AVP）和催产素。我们最近报道了抗酶抑制剂1（Azin 1），多胺合成的重要调节剂，在大鼠SON和PVN作为3天的脱水的结果的mRNA表达增加。在这里，我们表明，AZIN 1蛋白是高度表达的AVP和催产素阳性的大细胞神经元的SON和PVN与抗酶1（AZ 1），鸟氨酸脱羧酶，和多胺。脱水、盐负荷和急性高渗应激导致SON和PVN中Azin 1 mRNA表达增加。在器官型下丘脑文化，除了不可逆的鸟氨酸脱羧酶抑制剂DL-2-（二氟甲基）-鸟氨酸盐酸盐显着增加了丰富的异源AVP，但不是异源催产素。为了鉴定Azin 1在体内的功能，将过表达或敲低Azin 1的慢病毒载体立体定向递送到SON和/或PVN中。Azin 1短发夹RNA递送导致血浆渗透压降低，并对食物摄入有显著影响。Azin 1短发夹状RNA可显著上调视上核AVP mRNA的表达。相反，Azin 1在SON中的过表达降低AVP mRNA的表达。因此，我们已经确定了AZIN 1，并因此推断，多胺作为AVP基因表达的新调节剂。
The polyamines spermidine and spermine are small cations present in all living cells. In the brain, these cations are particularly abundant in the neurons of the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, which synthesize the neuropeptide hormones arginine vasopressin (AVP) and oxytocin. We recently reported increased mRNA expression of antizyme inhibitor 1 (Azin1), an important regulator of polyamine synthesis, in rat SON and PVN as a consequence of 3 days of dehydration. Here we show that AZIN1 protein is highly expressed in both AVP- and oxytocin-positive magnocellular neurons of the SON and PVN together with antizyme 1 (AZ1), ornithine decarboxylase, and polyamines. Azin1 mRNA expression increased in the SON and PVN as a consequence of dehydration, salt loading, and acute hypertonic stress. In organotypic hypothalamic cultures, addition of the irreversible ornithine decarboxylase inhibitor DL-2-(difluoromethyl)-ornithine hydrochloride significantly increased the abundance of heteronuclear AVP but not heteronuclear oxytocin. To identify the function of Azin1 in vivo, lentiviral vectors that either overexpress or knock down Azin1 were stereotaxically delivered into the SON and/or PVN. Azin1 short hairpin RNA delivery resulted in decreased plasma osmolality and had a significant effect on food intake. The expression of AVP mRNA was also significantly increased in the SON by Azin1 short hairpin RNA. In contrast, Azin1 overexpression in the SON decreased AVP mRNA expression. We have therefore identified AZIN1, and hence by inference, polyamines as novel regulators of the expression of the AVP gene.