title: Regulation of PGI2 activity by serum proteins: serum albumin but not high density lipoprotein is the PGI2 binding and stabilizing protein in human blood.
abstract: Although previous studies have shown that serum albumin binds PGI2 and protects it from rapid degradation, it remains debatable whether it is physiologically important due to its low binding affinity for PGI2. We were intrigued by the observations of Yui et al. (J. Clin. Invest. 82 (1988) 803-807) which suggested that apo A-I of the high density lipoprotein (HDL) is the "serum PGI2 stabilizing factor". To clarify this, we carried out experiments to determine the binding kinetics and parameters of HDL and albumin purified from normal pooled human serum. Despite the use of multiple binding assays, we could not detect any binding activity in HDL2, HDL3 or nascent HDL preparations, nor could we demonstrate any PGI2 protecting activity by these molecules. By contrast, purified albumin exhibited essentially identical binding parameters as the native serum from which the albumin was purified. The binding activity of various albumin preparations was not due to the contamination of apo A-I. Computer simulation analysis also failed to provide evidence to support the notion that HDL bound and prolonged PGI2 activity. To determine whether physiological concentrations of albumin influence PGI2 binding to platelet receptors, we measured PGI2 binding to platelet membrane in the absence and presence of albumin. Albumin at 40 mg/ml increased the KD of PGI2 binding to the receptors by 2-3 fold. These findings indicate that albumin plays a major role in protecting PGI2 activity and regulating its availability for platelet PGI2 receptors.
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center, Houston, TX 77225.
authors.forename: A L
authors.initials: AL
authors.lastname: Tsai
authors.forename: M J
authors.initials: MJ
authors.lastname: Hsu
authors.forename: W
authors.initials: W
authors.lastname: Patsch
authors.forename: K K
authors.initials: KK
authors.lastname: Wu
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D001665:Binding Sites; D001682:Biological Availability; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011464:Epoprostenol / Q000097:blood*; D006207:Half-Life; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012709:Serum Albumin / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D012709:Serum Albumin; D011464:Epoprostenol