Haptoglobin binds the antiatherogenic protein apolipoprotein E - impairment of apolipoprotein E stimulation of both lecithin:cholesterol acyltransferase activity and cholesterol uptake by hepatocytes


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Abstract

Haptoglobin (Hpt) binds apolipoprotein A-I (ApoA-I), and impairs its stimulation of lecithin:cholesterol acyltransferase (LCAT). LCAT plays a major role in reverse cholesterol transport (RCT). Apolipoprotein E (ApoE), like ApoA-I, promotes different steps of RCT, including LCAT stimulation. ApoE contains amino acid sequences that are homologous with the ApoA-I region bound by Hpt and are involved in the interaction with LCAT. Therefore, Hpt was expected to also bind ApoE, and inhibit the ApoE stimulatory effect on LCAT. Western blotting and ELISA experiments demonstrated that the Hpt β-subunit binds ApoE. The affinity of Hpt for ApoE was higher than that for ApoA-I. High ratios of Hpt with either apolipoprotein, such as those associated with the acute phase of inflammation, inhibited, in vitro, the stimulatory effect of ApoE on the cholesterol esterification activity of LCAT. Hpt also impaired human hepatoblastoma-derived cell uptake of [3H]cholesterol from proteoliposomes containing ApoE or ApoA-I. We suggest that the interaction between Hpt and ApoE represents a mechanism by which inflammation affects atherosclerosis progression. Hpt might influence ApoE function in processes other than RCT.Structured digital abstractMINT-7258778: Hpt beta chain (uniprotkb:P00738) binds (MI:0407) to APOE (uniprotkb:P02649) by filter binding (MI:0049)MINT-7258829, MINT-7258868: Hpt (uniprotkb:P00738) binds (MI:0407) to APOA1 (uniprotkb:P02647) by competition binding (MI:0405)MINT-7258848, MINT-7258819, MINT-7258877: APOE (uniprotkb:P02649) binds (MI:0407) to Hpt (uniprotkb:P00738) by competition binding (MI:0405)MINT-7258791: Hpt (uniprotkb:P00738) binds (MI:0407) to APOE (uniprotkb:P02649) by pull down (MI:0096)MINT-7258760: Hpt (uniprotkb:P00738) physically interacts (MI:0915) with APOE (uniprotkb:P02649) by pull down (MI:0096)MINT-7258811: Hpt (uniprotkb:P00738) binds (MI:0407) to APOA1 (uniprotkb:P02647) by enzyme linked immunosorbent assay (MI:0411)MINT-7258801: Hpt (uniprotkb:P00738) binds (MI:0407) to APOE (uniprotkb:P02649) by enzyme linked immunosorbent assay (MI:0411)

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