Apolipoprotein A-I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high-density lipoproteins assembled by ABCA1 and LCAT.
Apolipoprotein A-I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high-density lipoproteins assembled by ABCA1 and LCAT.
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DOI：
10.1002/1873-3468.13950
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发表时间：
2021-03
期刊：
影响因子：
3.5
通讯作者：
Remaley AT
中科院分区：
文献类型：
--
作者：
Tsujita M;Vaisman B;Chengyu L;Vickers KC;Okuhira KI;Braesch-Andersen S;Remaley AT
载脂蛋白A-I是高密度脂蛋白（HDL）的主要结构蛋白，尽管在脑细胞中缺乏表达，但存在于人和小鼠的脑脊液（CSF）中。为了鉴定CSF中apoA-I的来源，我们产生了精氨酸特异性和肝脏特异性Apoa 1敲除小鼠（分别为Apoa 1 ΔInt和Apoa 1 Δliv小鼠）。Apoa 1 ΔInt和Apoa 1 ΔLiv小鼠的脂蛋白谱与对照同窝小鼠相似，而在肠道和肝脏中敲除Apoa 1（Apoa 1 ΔIntΔLiv）导致HDL胆固醇水平降低60%，因此强烈模仿Apoa 1 −/−小鼠。免疫分析显示Apoa 1 ΔIntΔLiv小鼠的CSF中不存在小鼠apoA-I。此外，CSF中apoA-I水平与血浆球形HDL水平高度相关，其受ABCA 1和LCAT调节。总的来说，这些结果表明CSF中的apoA-I蛋白起源于肝脏和小肠，并从血浆中摄取。
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 (Apoa1ΔInt and Apoa1Δliv mice, respectively). Lipoprotein profiles of Apoa1ΔInt and Apoa1ΔLiv mice resembled those of control littermates, whereas knockout of Apoa1 in both intestine and liver (Apoa1ΔIntΔLiv) 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 Apoa1ΔIntΔLiv 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.
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