Apolipoprotein A‐I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high‐density lipoproteins assembled by ABCA1 and LCAT
| Autor: | Liu Chengyu, Alan T. Remaley, Kasey C. Vickers, Kei‐ichiro Okuhira, Sten Braesch‐Andersen, Boris L. Vaisman, Maki Tsujita |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Apolipoprotein B Biophysics High density Biochemistry Article Phosphatidylcholine-Sterol O-Acyltransferase Mice Cerebrospinal fluid Structural Biology Internal medicine Genetics medicine Animals Intestinal Mucosa Molecular Biology Mice Knockout Apolipoprotein A-I biology Chemistry nutritional and metabolic diseases Cell Biology Small intestine Endocrinology medicine.anatomical_structure Liver ABCA1 Knockout mouse Lecithin—cholesterol acyltransferase biology.protein lipids (amino acids peptides and proteins) Lipoproteins HDL ATP Binding Cassette Transporter 1 Lipoprotein |
| Zdroj: | FEBS Lett |
| ISSN: | 1873-3468 0014-5793 |
| Popis: | 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(ΔInt) and Apoa1(Δliv) mice, respectively). Lipoprotein profiles of Apoa1(ΔInt) and Apoa1(ΔLiv) mice resembled those of control littermates, whereas knockout of Apoa1 in both intestine and liver (Apoa1(ΔIntΔLiv)) 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(ΔIntΔLiv) 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. |
| Databáze: | OpenAIRE |
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