Colocalization of a carnosine-splitting enzyme, tissue carnosinase (CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine decarboxylase in the tuberomammillary nucleus of the hypothalamus
Colocalization of a carnosine-splitting enzyme, tissue carnosinase (CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine decarboxylase in the tuberomammillary nucleus of the hypothalamus
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DOI：
10.1016/j.neulet.2008.09.008
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发表时间：
2008-11
影响因子：
2.5
通讯作者：
H. Otani;A. Okumura;K. Nagai;Nobuaki Okumura
中科院分区：
文献类型：
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作者：
H. Otani;A. Okumura;K. Nagai;Nobuaki Okumura
肌肽是一种天然存在的二肽（β-丙氨酰-l-组氨酸），存在于哺乳动物组织如脑和骨骼肌中。肌肽不仅是一种自由基清除剂，而且可能是一种神经递质样分子，调节神经元功能，如下丘脑对自主神经系统的控制。CN 2（CNDP 2）是一种胞质酶，可水解肌肽以产生L-组氨酸和β-丙氨酸。为了了解肌肽和CN 2在脑中的功能，我们研究了CN 2在下丘脑中的免疫组织化学定位。CN 2-免疫反应高度集中在神经元细胞的背侧部分的结节乳头核的后下丘脑。由于结节乳头核是组胺能神经元的唯一来源，我们进一步研究了CN 2是否存在于组胺能神经元中。我们发现，CN 2-免疫反应共定位与组氨酸脱羧酶，这是组胺生物合成的关键酶，具体表达在结节乳头核的组胺能神经元。这些结果表明，CN 2在结节乳头核的组胺能神经元中高度表达，这意味着它可能为组胺能神经元提供组胺合成所需的组氨酸。
Carnosine is a naturally occurring dipeptide (β-alanyl-l-histidine) present in mammalian tissues such as the brain and skeletal muscles. Carnosine is not only a radical scavenger but also a possible neurotransmitter-like molecule that regulates neuronal functions such as hypothalamic control of the autonomic nervous system. CN2 (CNDP2) is a cytosolic enzyme that can hydrolyze carnosine to yield l-histidine and β-alanine. In order to understand the functions of carnosine and CN2 in the brain, we have investigated the immunohistochemical localization of CN2 in the hypothalamus. CN2-immunoreactivity was highly concentrated in neuronal cells in the dorsal part of the tuberomammillary nucleus of the posterior hypothalamus. Since the tuberomammillary nucleus is the exclusive origin of histaminergic neurons, we further investigated whether CN2 is present in the histaminergic neurons. We found that CN2-immunoreactivity was colocalized with that of histidine decarboxylase, which is the key enzyme for histamine biosynthesis specifically expressed in the histaminergic neurons of the tuberomammillary nucleus. These results suggest that CN2 is highly expressed in the histaminergic neurons in the tuberomammillary nucleus, implying that it may supply histidine to histaminergic neurons for histamine synthesis.