Human serum albumin

About: Human serum albumin is a research topic. Over the lifetime, 9402 publications have been published within this topic receiving 269029 citations. The topic is also known as: serum albumin & ALB.

Serum albumin is a specific inhibitor of apoptosis in human endothelial cells

Abstract: Excess blood vessels are removed by apoptosis of endothelial cells, however, the signals responsible for this have not been defined. Apoptosis of cultured human umbilical vein endothelial cells is induced by deprivation of serum or adhesion. In this paper, apoptosis in human umbilical vein and microvascular endothelium was induced by deprivation of serum and or adhesion. Apoptosis was confirmed on the basis of morphology, ultrastructure and internucleosomal cleavage of DNA. Loss of endothelial adhesion was found to be an early event in cultured endothelial cell apoptosis and was exploited to quantitate apoptosis. The effect of: bovine serum albumin; human serum albumin; recombinant human albumin; dithiothreitol reduced human and bovine albumin; CNBr treated human and bovine albumin as well as ovalbumin upon endothelial apoptosis was determined. Native bovine and human albumin as well as recombinant human material inhibited apoptosis at physiological concentrations with identical dose response curves in both umbilical vein and microvascular cells. Dithiothreitol treatment destroyed all protective activity while bovine but not human albumin was partially inactivated by CNBr treatment. The unrelated protein ovalbumin was not protective. Albumin did not inhibit apoptosis if cells were also deprived of adhesion. The data suggest that albumin is a specific inhibitor of human endothelial apoptosis but does not protect cells also deprived of adhesion. Reduced supply of albumin to endothelium in poorly perfused blood vessels may provide a mechanism for the removal of excess blood vessels in remodelling tissues. Also, the failure of albumin to protect endothelial cells deprived of adhesion from apoptosis may reflect the need to remove potentially micro-embolic cells detached due to trauma.

Albumin as a zinc carrier: properties of its high-affinity zinc-binding site

Abstract: Although details of the molecular mechanisms for the uptake of the essential nutrient zinc into the bloodstream and its subsequent delivery to zinc-requiring organs and cells are poorly understood, it is clear that in vertebrates the majority of plasma zinc (9–14 μM; approx. 75–85%) is bound to serum albumin, constituting part of the so-called exchangeable pool. The binding of metal ions to serum albumins has been the subject of decades of studies, employing a multitude of techniques, but only recently has the identity and putative structure of the major zinc site on albumin been reported. Intriguingly, this site is located at the interface between two domains, and involves two residues from each of domains I and II. Comparisons of X-ray crystal structures of free and fatty-acid bound human serum albumin suggest that zinc binding to this site and fatty acid binding to one of the five major sites may be interdependent. Interactive binding of zinc and long-chain fatty acids to albumin may therefore have physiological implications.

Role of arg-410 and tyr-411 in human serum albumin for ligand binding and esterase-like activity.

Abstract: Recombinant wild-type human serum albumin (rHSA), the single-residue mutants R410A, Y411A, Y411S and Y411F and the double mutant R410A/Y411A were produced using a yeast expression system. The recombinant proteins were correctly folded, as they had the same stability towards guanidine hydrochloride and the same CD spectrum as HSA isolated from serum (native HSA). Thus the global structures of the recombinant proteins are probably very similar to that of native HSA. We investigated, by ultrafiltration and CD, the high-affinity binding of two representative site II ligands, namely ketoprofen and diazepam. According to the crystal structure of HSA, the residues Arg-410 and Tyr-411 protrude into the centre of site II (in subdomain 3A), and the binding results showed that the guanidino moiety of Arg-410, the phenolic oxygen and the aromatic ring of Tyr-411 are important for ketoprofen binding. The guanidino moiety probably interacts electrostatically with the carboxy group of ketoprofen, the phenolic oxygen could make a hydrogen-bond with the keto group of the ligand, and the aromatic ring may participate in a specific stacking interaction with one of or both of the aromatic rings of ketoprofen. By contrast, Arg-410 is not important for diazepam binding. The two parts of Tyr-411 interact favourably with diazepam, and probably do so in the same way as with ketoprofen. In addition to its unique ligand binding properties, HSA also possesses an esterase-like activity, and studies with p-nitrophenyl acetate as a substrate showed that, although Arg-410 is important, the enzymic activity of HSA is much more dependent on the presence of Tyr-411. A minor activity could be registered when serine, but not alanine or phenylalanine, was present at position 411.