Description Descrizione: Apolipoprotein A1 (ApoA1) is the major component of the high density lipoproteins (HDL) which play an important role in the reverse cholesterol transport. In particular, ApoA1 stimulates the efflux of cholesterol from cell toward HDL, and the enzyme lecithin-cholesterol acyltransferase (LCAT) to convert, on the HDL surface, cell-derived cholesterol into cholesteryl ester, which is then placed into the lipoprotein core and transported through circulation to liver for catabolism and bile production. Haptoglobin (Hpt) binds to ApoA1 and inhibits the ApoA1-dependent activity of LCAT. Hpt is long far known to capture and transport to the liver free Hemoglobin in the pathway of iron recycling for erythropoiesis. Hpt is one of the most abundant proteins in the plasma and its level increases more than ten times during inflammation processes. Hpt-dependent masking of the ApoA1 site involved in the LCAT stimulation was suggested to be responsible for decreased LCAT activity. Thus, high Hpt levels, as present in the acute phase of inflammation, might impair cholesterol removal from peripheral cells, including vascular cells, and play an important role in worsening vascular endothelial dysfunction and accelerating atherosclerosis. Using a combination of protein chemical fragmentation and peptide synthesis techniques we mapped the Hpt? binding site of Apo A? I. Peptides reproducing this region are able to compete with ApoA? I for binding to Hpt and effectively restore the LCAT activity in the presence of Hpt in vitro and in vivo. These peptides might be used for treatment of diseases associated with defective reverse cholesterol transport. Currently, we are highlighting the role of each residue involved in Hpt recognition and designing new derivatives
Selected papers Lavori selezionati: 1) Spagnuolo MS, Cigliano L, DAndrea LD, Pedone C, Abrescia P Assignment of the binding site for Haptoglobin on Apolipoprotein A-I J. Biol. Chem. (2005), 280, 1193-11982) Cigliano L, D'Andrea LD, Maresca B, Serino M, Carlucci A, Salvatore A, Spagnuolo MS, Scigliuolo G, Pedone C, Abrescia P Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the Apolipoprotein A-I binding site for Haptoglobin Biol. Chem 2008, 389, 1421-14263) Bucci RM, Cigliano L, Vellecco V, D'Andrea LD, Ziaco B, Rossi A, Sautebin L, Carlucci A, Abrescia P, Pedone C, Ianaro A, Cirino G ApoA-I mimetic peptide P2a by restoring cholesterol esterification unmasks Apo A-I anti-inflammatory endogenous activity in vivo J. Pharm. Exp. Ther. 20124) P. Abrescia et al., PCT/IT2005/403
249 Records (222 escludendo Abstract e Conferenze). Impact factor totale: 754.696 (685.645 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 786.791 (709.858 escludendo Abstract e Conferenze).