Haptoglobin binds the antiatherogenic protein apolipoprotein E - impairment of apolipoprotein E stimulation of both lecithin:cholesterol acyltransferase activity and cholesterol uptake by hepatocytes.
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 beta-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 [(3)H]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.
Cigliano
Luisa
L
Dipartimento delle Scienze Biologiche, Università di Napoli Federico II, Italy.
Pugliese
Carmela R
CR
Spagnuolo
Maria S
MS
Palumbo
Rosanna
R
Abrescia
Paolo
P
D016632:Apolipoprotein A-I / Q000378:metabolism; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000517:prevention & control*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D006242:Haptoglobins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D006242:Haptoglobins; D006454:Hemoglobins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase