Haptoglobin binds apolipoprotein E and influences cholesterol esterification in the cerebrospinal fluid.
Haptoglobin (Hpt) binds the apolipoprotein (Apo) A-I domain, which is involved in stimulating the enzyme lecithin-cholesterol acyltransferase (LCAT) for cholesterol esterification. This binding was shown to protect ApoA-I against hydroxyl radicals, thus preventing loss of ApoA-I function in enzyme stimulation. In this study, we report that Hpt is also able to bind ApoE. The Hpt binding site on the ApoE structure was mapped by using synthetic peptides, and found homologous to the Hpt binding site of ApoA-I. Hydroxyl radicals promoted in vitro the formation of ApoE-containing adducts which were detected by immunoblotting. Hpt impaired this oxidative modification whereas albumin did not. CSF from patients with multiple sclerosis or subjects without neurodegeneration contains oxidized forms of ApoE and ApoA-I similar to those observed in vitro. CSF was analyzed for its level of ApoA-I, ApoE, Hpt, cholesteryl esters, and unesterified cholesterol. The ratio of esterified with unesterified cholesterol, assumed to reflect the LCAT activity ex vivo, did not correlate with either analyzed protein, but conversely correlated with the ratio [Hpt]/([ApoE]+[ApoA-I]). The results suggest that Hpt might save the function of ApoA-I and ApoE for cholesterol esterification, a process contributing to cholesterol elimination from the brain.
Salvatore
Alfonso
A
Dipartimento delle Scienze Biologiche Università di Napoli Federico II, Mezzocannone, Napoli, Italia.
Cigliano
Luisa
L
Carlucci
Alessandro
A
Bucci
Enrico M
EM
Abrescia
Paolo
P
D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004951:Esterification / Q000502:physiology*; D006242:Haptoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000503:physiopathology; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid / Q000503:physiopathology; D009448:Neurochemistry / Q000379:methods; D011485:Protein Binding / Q000502:physiology
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D006242:Haptoglobins; D002784:Cholesterol