Multiple plasma proteins control atrial natriuretic peptide (ANP) aggregation.
We have recently demonstrated that human alpha-atrial natriuretic peptide (alpha-hANP), an amyloidogenic peptide responsible for isolated atrial amyloidosis, binds to a dimeric form of apo A-I belonging to small high-density lipoproteins (HDL). This binding phenomenon is considered a protective mechanism since it inhibits or strongly reduces the ANP aggregation process. The observation that plasma exhibits at least four times greater amyloid inhibitory activity than HDL prompted us to determine whether small HDL are the only ANP plasma-binding factors. After incubation of whole plasma with labelled ANP, the macromolecular complexes were subjected to two-dimensional gel electrophoresis followed by autoradiography. The results presented here provide novel evidence of additional binding proteins, in addition to apo A-I dimer, able to bind ANP in vitro and to prevent its aggregation. The mass spectrometry analysis of the radioactive spots identified them as albumin, alpha-1 antitrypsin, orosomucoid and apo A-IV-TTR complex. The putative impact of these findings in the amyloidogenic/antiamyloidogenic peptides network is discussed.
Torricelli
C
C
Department of Physiology, University of Siena, via Aldo Moro, 53100 Siena, Italy.
Capurro
E
E
Santucci
A
A
Paffetti
A
A
D'Ambrosio
C
C
Scaloni
A
A
Maioli
E
E
Pacini
A
A
D000686:Amyloidosis / Q000097:blood; D016632:Apolipoprotein A-I / Q000032:analysis / Q000378:metabolism; D001054:Apolipoproteins A / Q000032:analysis / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D019281:Dimerization; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D009961:Orosomucoid / Q000032:analysis / Q000378:metabolism; D011228:Prealbumin / Q000032:analysis / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000378:metabolism
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001798:Blood Proteins; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D009961:Orosomucoid; D011228:Prealbumin; C043392:SERPINA1 protein, human; D012709:Serum Albumin; D000515:alpha 1-Antitrypsin; C022205:apolipoprotein A-IV; D009320:Atrial Natriuretic Factor