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Publication : Apolipoprotein A-I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high-density lipoproteins assembled by ABCA1 and LCAT.

First Author  Tsujita M Year  2021
Journal  FEBS Lett Volume  595
Issue  6 Pages  773-788
PubMed ID  33020907 Mgi Jnum  J:305409
Mgi Id  MGI:6705040 Doi  10.1002/1873-3468.13950
Citation  Tsujita M, et al. (2021) Apolipoprotein A-I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high-density lipoproteins assembled by ABCA1 and LCAT. FEBS Lett 595(6):773-788
abstractText  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(DeltaInt) and Apoa1(Deltaliv) mice, respectively). Lipoprotein profiles of Apoa1(DeltaInt) and Apoa1(DeltaLiv) mice resembled those of control littermates, whereas knockout of Apoa1 in both intestine and liver (Apoa1(DeltaIntDeltaLiv) ) 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(DeltaIntDeltaLiv) 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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