Abstract
The high-density lipoprotein apolipoprotein A-I (ApoA-I) stimulates the enzyme lecithin-cholesterol acyltransferase (LCAT) in the reverse cholesterol transport pathway. Two ApoA-I variants, Zaragoza (L144R) and Zavalla (L159P), are associated with low levels of HDL-cholesterol but normal LCAT activity. Haptoglobin interacts with ApoA-I, impairing LCAT stimulation. Synthetic peptides matching the haptoglobin-binding site of native or variant ApoA-I (native, P2a; variants, Zav-pep and Zar-pep) bound haptoglobin with different activity: Zar-pep>P2a>Zav-pep. They also differently rescued LCAT in vitro activity in the presence of haptoglobin (P2a=Zar-pep>Zav-pep). Therefore, both amino acid conversions affect haptoglobin binding and LCAT regulation. We highlight the role of haptoglobin in LCAT regulation in subjects with ApoA-I variants.
| Original language | English |
|---|---|
| Pages (from-to) | 1421-1426 |
| Number of pages | 6 |
| Journal | Biological Chemistry |
| Volume | 389 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2008 |
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Keywords
- ApoA-I Zaragoza
- ApoA-I Zavalla
- High-density lipoprotein
- Lecithin-cholesterol acyltransferase
- Peptides
- Reverse cholesterol transport
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
Cite this
Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin. / Cigliano, Luisa; D'Andrea, Luca D.; Maresca, Bernardetta; Serino, Milena; Carlucci, Alessandro; Salvatore, Alfonso; Spagnuolo, Maria Stefania; Scigliuolo, Graziana; Pedone, Carlo; Abrescia, Paolo.
In: Biological Chemistry, Vol. 389, No. 11, 01.11.2008, p. 1421-1426.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin
AU - Cigliano, Luisa
AU - D'Andrea, Luca D.
AU - Maresca, Bernardetta
AU - Serino, Milena
AU - Carlucci, Alessandro
AU - Salvatore, Alfonso
AU - Spagnuolo, Maria Stefania
AU - Scigliuolo, Graziana
AU - Pedone, Carlo
AU - Abrescia, Paolo
PY - 2008/11/1
Y1 - 2008/11/1
N2 - The high-density lipoprotein apolipoprotein A-I (ApoA-I) stimulates the enzyme lecithin-cholesterol acyltransferase (LCAT) in the reverse cholesterol transport pathway. Two ApoA-I variants, Zaragoza (L144R) and Zavalla (L159P), are associated with low levels of HDL-cholesterol but normal LCAT activity. Haptoglobin interacts with ApoA-I, impairing LCAT stimulation. Synthetic peptides matching the haptoglobin-binding site of native or variant ApoA-I (native, P2a; variants, Zav-pep and Zar-pep) bound haptoglobin with different activity: Zar-pep>P2a>Zav-pep. They also differently rescued LCAT in vitro activity in the presence of haptoglobin (P2a=Zar-pep>Zav-pep). Therefore, both amino acid conversions affect haptoglobin binding and LCAT regulation. We highlight the role of haptoglobin in LCAT regulation in subjects with ApoA-I variants.
AB - The high-density lipoprotein apolipoprotein A-I (ApoA-I) stimulates the enzyme lecithin-cholesterol acyltransferase (LCAT) in the reverse cholesterol transport pathway. Two ApoA-I variants, Zaragoza (L144R) and Zavalla (L159P), are associated with low levels of HDL-cholesterol but normal LCAT activity. Haptoglobin interacts with ApoA-I, impairing LCAT stimulation. Synthetic peptides matching the haptoglobin-binding site of native or variant ApoA-I (native, P2a; variants, Zav-pep and Zar-pep) bound haptoglobin with different activity: Zar-pep>P2a>Zav-pep. They also differently rescued LCAT in vitro activity in the presence of haptoglobin (P2a=Zar-pep>Zav-pep). Therefore, both amino acid conversions affect haptoglobin binding and LCAT regulation. We highlight the role of haptoglobin in LCAT regulation in subjects with ApoA-I variants.
KW - ApoA-I Zaragoza
KW - ApoA-I Zavalla
KW - High-density lipoprotein
KW - Lecithin-cholesterol acyltransferase
KW - Peptides
KW - Reverse cholesterol transport
UR - http://www.scopus.com/inward/record.url?scp=56549094997&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56549094997&partnerID=8YFLogxK
U2 - 10.1515/BC.2008.156
DO - 10.1515/BC.2008.156
M3 - Article
C2 - 18783334
AN - SCOPUS:56549094997
VL - 389
SP - 1421
EP - 1426
JO - Biological Chemistry
JF - Biological Chemistry
SN - 1431-6730
IS - 11
ER -