Distribution and quantitative analysis of homoanserine and its 2-oxo derivative in mouse tissues
Distribution and quantitative analysis of homoanserine and its 2-oxo derivative in mouse tissues
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DOI：
10.1080/10715762.2021.1888945
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发表时间：
2021-07-08
影响因子：
3.3
通讯作者：
Ihara, Hideshi
中科院分区：
文献类型：
--
作者：
Kakihana, Yuki;Kasamatsu, Shingo;Ihara, Hideshi
含咪唑的二肽（IDP），如肌肽和鹅肌肽，是内源性产生的，并已被证明具有抗氧化剂的功能。最近，我们的特点是内源性生产的2-氧代咪唑的二肽（2-oxo-IDPs），如2-oxo-carnosine，2-oxo-anserine，和2-oxo-homocarnosine在小鼠组织，包括大脑，并证明2-oxo-IDPs表现出更高的抗氧化活性比相应的IDPs。本研究建立了一种高灵敏度、特异性和定量的液相色谱-串联质谱联用稳定同位素稀释法检测IDP高鹅丝氨酸及其氧化衍生物2-氧代高鹅丝氨酸的方法，并定量分析了其在C57 BL/6 J小鼠体内的组织分布和年龄相关的脑内分布。定量分析表明，高鹅丝氨酸不仅在小鼠脑中含量丰富，而且在其他组织如肌肉和肺中也有丰富的分布。此外，我们成功地检测到内源性生产的2-氧代高鹅丝氨酸在小鼠脑中。质谱分析表明，高鹅丝氨酸主要存在于大脑和小脑中，10周龄小鼠的浓度约为1周龄小鼠的50倍。因此，这是第一个研究，报告的空间和时间的表达模式的高鹅丝氨酸及其2-氧代衍生物在C57 BL/6 J小鼠。
Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are endogenously produced and have been shown to function as antioxidants. Recently, we have characterized the endogenous production of 2-oxo-imidazole-containing dipeptides (2-oxo-IDPs), such as 2-oxo-carnosine, 2-oxo-anserine, and 2-oxo-homocarnosine in mouse tissues, including brain, and demonstrated that 2-oxo-IDPs exhibit higher antioxidant activities than the corresponding IDPs. In this study, we established a highly sensitive, specific, and quantitative method for the detection of the IDP homoanserine and its oxidized derivative 2-oxo-homoanserine via high-performance liquid chromatography tandem mass spectrometry coupled with a stable-isotope dilution method, and quantitatively analyzed its tissue distribution and age-related intra-brain distribution in C57BL/6J mice. The quantitative analysis revealed that homoanserine exists abundantly not only in the mouse brain but also in other tissues, such as the muscle and lungs. Further, we successfully detected the endogenous production of 2-oxo-homoanserine in the mouse brain. The mass spectrometric analysis revealed that homoanserine predominantly exists in the cerebrum and cerebellum and the concentrations in 10-week-old mice were approximately 50-fold higher than those in 1-week-old mice. Accordingly, this is the first study that reports the spatial and temporal expression patterns of homoanserine and its 2-oxo derivative in C57BL/6J mice.