tailieunhanh - Báo cáo khoa học: 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. | ễFEBS Journal Haptoglobin binds the antiatherogenic protein apolipoprotein E - impairment of apolipoprotein E stimulation of both lecithin cholesterol acyltransferase activity and cholesterol uptake by hepatocytes Luisa Cigliano1 Carmela R. Pugliese1 Maria S. Spagnuolo2 Rosanna Palumbo3 and Paolo Abrescia1 1 Dipartimento delle Scienze Biologiche Universita di Napoli Federico II Italy 2 Istituto per ilSistema Produzione Animale in Ambiente Mediterraneo Consiglio Nazionale delle Ricerche Napoli Italy 3 Istituto di Biostrutture e Bioimmagini Consiglio Nazionale delle Ricerche Napoli Italy Keywords apolipoprotein A-I apolipoprotein E haptoglobin high-density lipoprotein HDL lecithin cholesterolacyltransferase LCAT Correspondence P. Abrescia Dipartimento delle Scienze Biologiche University di Napoli Federico II via Mezzocannone 8 80134 Napoli Italia Fax 39 081 2535090 Tel 39 081 2535095 E-mail Received 12 May 2009 revised 27 July 2009 accepted 21 August 2009 doi 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 b-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 proteolipo-somes