载脂蛋白 A-I 存在于小鼠脑脊髓液中，来源于肝脏和肠道，通过 ABCA1 和 LCAT 组装的血浆高密度脂蛋白。
Apolipoprotein A-I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high-density lipoproteins assembled by ABCA1 and LCAT.
机构信息
Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD, USA.
出版信息
FEBS Lett. 2021 Mar;595(6):773-788. doi: 10.1002/1873-3468.13950. Epub 2020 Oct 20.
Apolipoprotein (apo) A-I, the major structural protein of high-density lipoprotein (HDL), is present in human and mouse cerebrospinal fluid (CSF) despite its lack of expression in brain cells. To identify the origin of apoA-I in CSF, we generated intestine-specific and liver-specific Apoa1 knockout mice (Apoa1 and Apoa1 mice, respectively). Lipoprotein profiles of Apoa1 and Apoa1 mice resembled those of control littermates, whereas knockout of Apoa1 in both intestine and liver (Apoa1 ) resulted in a 60-percent decrease in HDL-cholesterol levels, thus strongly mimicking the Apoa1 mice. Immunoassays revealed that mouse apoA-I was not present in the CSF of the Apoa1 mice. Furthermore, apoA-I levels in CSF were highly correlated with plasma spherical HDL levels, which were regulated by ABCA1 and LCAT. Collectively, these results suggest that apoA-I protein in CSF originates in liver and small intestine and is taken up from the plasma.
载脂蛋白 A-I（apoA-I）是高密度脂蛋白（HDL）的主要结构蛋白，尽管其在脑细胞中无表达，但存在于人及鼠的脑脊液（CSF）中。为明确 CSF 中 apoA-I 的来源，我们构建了肠特异性和肝特异性 Apoa1 敲除小鼠（分别为 Apoa1 和 Apoa1 小鼠）。Apoa1 和 Apoa1 小鼠的脂蛋白谱与对照同窝仔鼠相似，而同时敲除肠和肝中的 Apoa1（Apoa1 ）导致 HDL-胆固醇水平降低 60%，因而强烈模拟 Apoa1 小鼠。免疫分析显示 Apoa1 小鼠的 CSF 中不存在鼠 apoA-I。此外，CSF 中的 apoA-I 水平与血浆球形 HDL 水平高度相关，后者受 ABCA1 和 LCAT 调节。综上，这些结果提示 CSF 中的 apoA-I 蛋白来源于肝和小肠，并从血浆中摄取。
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