Human FABP1 T94A variant enhances cholesterol uptake

Biochimica Et Biophysica Acta
Huan HuangFriedhelm Schroeder

Abstract

Although expression of the human liver fatty acid binding protein (FABP1) T94A variant alters serum lipoprotein cholesterol levels in human subjects, nothing is known whereby the variant elicits these effects. This issue was addressed by in vitro cholesterol binding assays using purified recombinant wild-type (WT) FABP1 T94T and T94A variant proteins and in cultured primary human hepatocytes expressing the FABP1 T94T (genotyped as TT) or T94A (genotyped as CC) proteins. The human FABP1 T94A variant protein had 3-fold higher cholesterol-binding affinity than the WT FABP1 T94T as shown by NBD-cholesterol fluorescence binding assays and by cholesterol isothermal titration microcalorimetry (ITC) binding assays. CC variant hepatocytes also exhibited 30% higher total FABP1 protein. HDL- and LDL-mediated NBD-cholesterol uptake was faster in CC variant than TT WT human hepatocytes. VLDL-mediated uptake of NBD-cholesterol did not differ between CC and TT human hepatocytes. The increased HDL- and LDL-mediated NBD-cholesterol uptake was not associated with any significant change in mRNA levels of SCARB1, LDLR, CETP, and LCAT encoding the key proteins in lipoprotein cholesterol uptake. Thus, the increased HDL- and LDL-mediated NBD-choleste...Continue Reading

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Citations

Jan 17, 2017·Ecotoxicology and Environmental Safety·Gabor MaaszZsolt Pirger
Mar 1, 2017·Molecular & Cellular Proteomics : MCP·Xiaofang JiaZhenghong Yuan
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Nov 14, 2019·European Heart Journal·Oriol Iborra-EgeaAntoni Bayes-Genis
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Dec 17, 2021·Toxicologic Pathology·Santokh GillTerry Koerner

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