Abstract |
Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five patients with IDCM, 17 patients with ischemic left ventricle dysfunction (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb-ANT). Sixteen of the 45 (36%) IDCM patients showed AAb-ANT above controls. In immunoblots, AAb-ANT detected purified bovine heart ANT and GST-ANT1 and GST-ANT2 isoforms and, less frequently, the GST-ANT3 isoform. A construct lacking the last 146 amino acids did not react with AAb-ANT, indicating that the main epitopes are in the C-terminal 146 amino acids. Immunodetection of decapeptides covering this region shows that AAb-ANT detects at least three epitopes, demonstrating that ANT is the primary target of AAb-ANT. The most significant epitopes belong to the M2 and M3 hydrophilic loops of ANT suggesting that apart from being essential for its activity, these loops are highly immunogenic.
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Authors | Carlos Manchado, Josefina Orús, Francesc Villarroya, Eulalia Roig, Magda Heras, Marta Giralt, Roser Iglesias, Ginés Sanz, Teresa Mampel, Octavi Viñas |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 34
Issue 5
Pg. 571-82
(May 2002)
ISSN: 0022-2828 [Print] England |
PMID | 12056860
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2002 Academic Press. |
Chemical References |
- Autoantigens
- Protein Isoforms
- Recombinant Fusion Proteins
- Mitochondrial ADP, ATP Translocases
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Topics |
- Animals
- Autoantigens
(immunology)
- Cardiomyopathy, Dilated
(enzymology, immunology)
- Cattle
- Cloning, Molecular
- Enzyme-Linked Immunosorbent Assay
- Epitope Mapping
- Female
- Humans
- Immunoblotting
- Male
- Middle Aged
- Mitochondria
(immunology, metabolism)
- Mitochondrial ADP, ATP Translocases
(immunology)
- Protein Isoforms
- Rats
- Recombinant Fusion Proteins
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