The interaction of hydrophobic bile acids with the alpha 1-proteinase inhibitor.
An in vitro complex formation between cholesterol and human alpha 1-proteinase inhibitor (alpha 1-antitrypsin, alpha 1-Pi) has been described. Hydrophobic bile acids were studied for a similar interaction using lithocholic acid (LC) as a prototype of a hydrophobic acid. At a molar ratio of 5:1, LC induced conformational changes of alpha 1-Pi reflected in an abnormal gel-electrophoretic appearance, loss of anodal immunoreactivity on crossed immunoelectrophoresis, exposition of new antigenic determinant(s) on immunodiffusion, and loss of antiproteinase activity. After 6 h incubation, LC and alpha 1-Pi form a complex of approximately 200 kDa molecular mass seen following gel-filtration. After prolonged (24 h) interaction a series of large alpha 1-Pi polymers were seen on SDS-PAGE under reducing conditions followed by Western blotting. Glycolitho-, sulfolitho-, deoxycholic and 3-beta-hydroxy-5-cholenoic acids induced similar but less pronounced changes of alpha 1-Pi, whereas transferrin remained unaffected. Hydrophilic acids lacked effect on alpha 1-Pi. The results are compatible with a specific, irreversible interaction of alpha 1-Pi with hydrophobic bile acids affecting its physical and proteinase inhibitory properties. The cholestatic potency of the hydrophobic acids studied and their ability to induce alpha 1-Pi polymerization may be important in cholestatic conditions.
Janciauskiene
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Lund University, Department of Medicine, Malmö General Hospital, Sweden.
Eriksson
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D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D001704:Biopolymers; D015153:Blotting, Western; D002784:Cholesterol / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D011108:Polymers; D011487:Protein Conformation; D013552:Swine; D014867:Water / Q000737:chemistry; D000515:alpha 1-Antitrypsin / Q000737:chemistry*
D001647:Bile Acids and Salts; D001704:Biopolymers; D011108:Polymers; D000515:alpha 1-Antitrypsin; D014867:Water; D002784:Cholesterol