Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02079 (lysine)
 58,762 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors examined neosynthesis of fiber proteins (scleroproteins) in the aorta of rats with genetic hypertonia and with experimental atherosclerosis after application of 3H-proline and 3H-lysine and subsequent determination of radioactivity of collagenous and elastic in the aortic wall. There was a great increase in incorporation a labelled precursors of collagen and elastin in the aorta of hypertonic and atherosclerotic animals in comparison with the control rats-a manifestation of increased "de novo" synthesis of fiber proteins in rats with these arterial diseases. Furthermore the increased collagenosis dominated over that of elastogenesis. The irregularity in the activation of biosynthesis of both sclero-proteins in rats with hypertonia and atherosclerosis caused remodeling of macromolecular structure of the aretrial wall with a predominance of collagen over the remaining components of the connective tissue matrix. The resulting fibrosis of the arterial wall favoured the fixation of hypertonia and progression of atherosclerosis.
 ...
PMID:[Arterial scleroproteins in atherosclerosis and hypertension (experimental studies)]. 43 8

Elasticity and elastin of arteries in 106 dead people aged 14--74 years were investigated using physico-chemical methods. Depending on the character of morphological manifestations, aortas and arteries were divided into following groups: 1) without morphological manifestations of atherosclerosis; 2) affected by atherosclerosis; 3) vessels of patients who had suffered from atherosclerosis and hypertensive disease; 4) aortas and arteries of patients with atherosclerosis in combination with other somatic diseases. In atherosclerosis and hypertensive disease there were observed specific shifts in the character and intensity of fluorescence of elastin and elasticity as a whole. The intensity of primary fluorescence as an atherosclerotic process progressed and in concomitant hypertensive disease gradually changed. In atherosclerosis there were noted changes in transversal bands in elastin. The growth of transversal bands and intensity of fluorescence were found to be interrelated. Optical density of dissolved elastin with wave lengths (lambda) 240, 260, 280, 300, 320, 360, 400, 490 nm and pH 7.7 and 8.6 was studied. The peak of intensity of absorption of the solution of elastin in all groups referred to above was noted at the wave length lambda=240 nm. Amino-acid composition of dissolved elastin was also studied. It was established that as the process of atherosclerosis progressed, the content of lysine in the wall increased depending on the phase of the process -- lipoidosis, atheromatosis, etc. In the vascular wall there were observed changes in monoamino-oxidase, the latter being of particular importance for maintaining the level of cuprum in tissues.
 ...
PMID:[Arterial elastin in atherosclerosis and hypertensive disease]. 118 Jun 99

External jugular veins that had been subjected to the hemodynamic stresses produced by experimental arteriovenous anastomosis developed 2% increased total protein contents and 17% increased collagen contents. When the stressed veins were homogenized and extracted with saline solutions, statistically significant increases in the saline-soluble proteins and in the saline-soluble collagen (87% and 267%, respectively) were observed. Increased amounts of low molecular weight peptides were found in the extracts. A fraction of these peptides could be degraded by Clostridium collagenase. The saline extract also contained proteins which resembled by their amino-acid composition the acidic structural proteins of the connective tissues. Additonally, in 3 dogs so tested, changes were found in the hydroxylation and glycosylation of lysine from gelatin extracts as well as in the lysine and desmosine contents of the insoluble elastin fractions. This is the first demonstration of a hemodynamically induced increase in the saline solubility of connective tissue proteins in the absence of dietary manipulations.
Atherosclerosis
PMID:Hemodynamically-induced increase in soluble collagen in the anastomosed veins of experimental arteriovenous fistulae. 126 60

Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.
 ...
PMID:Autoantibody against oxidised LDL and progression of carotid atherosclerosis. 135 50

Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Lp(a) consists of a LDL-like moiety with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) has a high homology with plasminogen (Pg). In vivo, Pg is activated on a fibrin surface by tissue Pg activator (tPA). We prepared Lp(a) from plasma by sequential ultracentrifugation followed by lysine-sepharose affinity chromatography. We found that a changing (donor dependent) fraction of the Lp(a) did not bind to lysine-sepharose. This fraction, designated Lp(a)lys-, was further purified using gel filtration. Bound Lp(a) [Lp(a)lys+] was eluted with 0.2 M EACA. Apo(a) isoforms in both fractions were identical. In contrast Lp(a)lys+ inhibited Pg activation by tPA in vitro (IC50% 20 mg/l), whereas Lp(a)lys- did not. In addition Lp(a)lys- did not bind to CNBr-digested fibrinogen whereas Lp(a)lys+ did (Kd, app = 0.2 nM). Therefore we conclude that a changing donor dependent fraction of human plasma Lp(a) does not inhibit Pg activation in vitro and does not bind to CNBr-digested fibrinogen.
 ...
PMID:Lysine-binding heterogeneity of Lp(a): consequences for fibrin binding and inhibition of plasminogen activation. 141 65

We have previously shown that lipoprotein(a) [Lp(a)], an atherogenic lipoprotein that contains apolipoprotein(a), which shares partial structural homology to plasminogen, binds to a plasmin-modified fibrin surface, and we have postulated that this interaction may be atherogenic. Moderate elevations in blood homocysteine, a relatively common condition, predispose to premature atherosclerosis. The reasons for this are not established. We now report that homocysteine, at concentrations as low as 8 microM, significantly increases the affinity of Lp(a) for fibrin. Homocysteine induces a 20-fold increase in the affinity between Lp(a) and plasmin-treated fibrin and a 4-fold increase with unmodified fibrin. Lp(a) binding is inhibited by epsilon-aminocaproic acid, indicating lysine binding site specificity. Homocysteine does not enhance the binding of Lp(a) to other surface-bound proteins. Cysteine, glutathione, and N-acetylcysteine also increase the affinity between Lp(a) and fibrin. Homocysteine does not affect the binding of low density lipoprotein or plasminogen to fibrin, nor does it alter the gel-filtration elution pattern of Lp(a). Immunoblot analysis documents the fact that homocysteine partially reduces Lp(a). These results suggest that homocysteine alters the intact Lp(a) particle so as to increase the reactivity of the plasminogen-like apolipoprotein(a) portion of the molecule. The observation that sulfhydryl amino acids increase Lp(a) binding to fibrin suggests a biochemical relationship between sulfhydryl compound metabolism, thrombosis, and atherogenesis.
 ...
PMID:Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism. 143 9

The structural and compositional changes occurring during in vitro chemical modification of apolipoprotein B-100 (apo B), the apolipoprotein component of low density lipoproteins (LDL), were investigated in this study. The functional properties of chemically modified apo B and especially its potential to induce accumulation of cholesterol esters in macrophages were related to the structural changes of apo B. Acetylation, maleylation or malondialdehyde conjugation did not significantly affect the lipid composition of LDL. However, the unsaturated cholesteryl esters content, especially that of cholesteryl arachidonate was significantly decreased through Cu-oxidation. The number of reactive lysine residues in apo B was decreased by Cu-catalyzed LDL oxidation, acetylation, maleylation and by malondialdehyde conjugation. The number of free cysteines decreased from six in native apo B-100 to three in Cu-oxidized LDL. The tryptophan fluorescence intensity decreased most in malondialdehyde-conjugated LDL and in Cu-oxidized LDL, compared with acetylated and maleylated LDL. The secondary structure of native and chemically modified LDL was measured by attenuated total reflection infrared spectroscopy and by circular dichroism. No significant changes were observed in the secondary structure of any of the modified LDL. These data suggest that neither acetylation, malondialdehyde treatment or even Cu-oxidation substantially altered the secondary structure of apo B, in spite of significant modifications in the primary structure. Incubation of chemically modified LDL with J774 macrophages induced an accumulation of cellular cholesteryl esters and foam cell formation. The highest cholesterol accumulation was induced after malondialdehyde treatment of LDL. These data suggest that the cellular uptake and accumulation of modified LDL is not modulated by changes in the apo B structure. Rather it seems dependent upon the net charge of the apo B protein and probably involves the modification of critical lysine residues.
Atherosclerosis 1992 Dec
PMID:Structural and functional properties of apolipoprotein B in chemically modified low density lipoproteins. 146 63

The properties of sialylated (sialic acid rich) and desialylated (sialic acid poor) fractions of low-density lipoproteins (LDL) isolated from blood plasma of healthy subjects and coronary atherosclerosis patients have been investigated. Sialylated (60-90% of total LDL) and desialylated (10-40%) LDL were separated by affinity chromatography on Ricinus communis agglutinin-agarose. Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were found to be the same, and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated, ones. Desialylated, but not sialylated, LDL induced 1.5 to 4-fold accumulation of neutral lipids in human aortic smooth-muscle cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared to sialylated LDL. On the other hand, the concentrations of di-, monoglycerides and free fatty acids in desialylated LDL were 2 to 3-fold higher than in sialylated lipoproteins. The desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin and phosphatidylethanolamine, but a higher content of lysophosphatidylcholine. Levels of thiobarbituric acid-reactive substances in freshly isolated desialylated and sialylated LDL were the same. Desialylated LDL had a higher level of oxysterols and lower amounts of vitamins A and E. The content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. The results of this study demonstrate that multiple physico-chemical parameters of desialylated LDL differ from those of sialylated LDL.
 ...
PMID:Characterization of desialylated low-density lipoproteins which cause intracellular lipid accumulation. 147 92

Aminoguanidine decreases the formation of advanced glycosylation end products that occurs during chronic hyperglycemia. Presumably this occurs because early glycosylation products preferentially bind to aminoguanidine rather than to lysine groups of adjacent proteins. Because oxidative modification of low density lipoprotein (LDL) also involves derivatization of lysine residues of apolipoprotein (apo) B by reactive aldehydes formed during the decomposition of oxidized fatty acids, we postulated that aminoguanidine might also inhibit the oxidatively induced modification of LDL protein. To test this hypothesis we oxidized LDL by incubation with Cu2+ or with endothelial cells in the absence or presence of aminoguanidine. Aminoguanidine prevented apo B lysine modification, as measured by fluorescence spectroscopy, and inhibited in a dose-dependent manner the oxidatively induced increase in subsequent macrophage uptake. At concentrations that inhibited apo B modification (5-10 mM), aminoguanidine increased the lag time in diene conjugation but did not affect the plateau value reached. These data indicate that aminoguanidine inhibits oxidative modification of LDL protein in large part by binding reactive aldehydes formed during lipid peroxidation and preventing their subsequent conjugation to apo B. Thus, aminoguanidine (and related compounds) may be of dual benefit in inhibiting atherosclerosis, both by inhibiting formation of advanced glycosylation end products and by inhibiting the modification of LDL apo B that makes it a ligand for scavenger receptors.
 ...
PMID:Aminoguanidine inhibits oxidative modification of low density lipoprotein protein and the subsequent increase in uptake by macrophage scavenger receptors. 149 78

Changes in low density lipoprotein (LDL) lipid composition were shown to alter its interaction with the LDL receptor, thus affecting its cellular uptake. Upon incubation of LDL with 5 units/ml cholesterol esterase (CEase) for 1 h at 37 degrees C, there was a 33% reduction in lipoprotein cholesteryl ester content, paralleled by an increment in its unesterified cholesterol. CEase-LDL, in comparison to native LDL, was smaller in size, possessed fewer free lysine amino groups (by 14%), and demonstrated reduced binding to heparin (by 83%) and reduced immunoreactivity against monoclonal antibodies directed toward epitopes along the LDL apoB-100. Incubation of CEase-LDL with the J-774 macrophage-like cell line resulted in about a 30% reduction in lipoprotein binding and degradation in comparison to native LDL, and this was associated with a 20% reduction in macrophage cholesterol mass. Similarly, CEase-LDL degradation by mouse peritoneal macrophages, human monocyte-derived macrophages, and human skin fibroblasts was reduced by 20-44% in comparison to native LDL. CEase-LDL uptake by macrophages was mediated via the LDL receptor and not the scavenger receptor. CEase activity toward LDL was demonstrated in plasma and in cells of the arterial wall such as macrophages and endothelial cells. Thus, CEase modification of LDL may take place in vivo, and this phenomenon may have a role in atherosclerosis.
 ...
PMID:Reduced uptake of cholesterol esterase-modified low density lipoprotein by macrophages. 171 Oct 36


1 2 3 4 5 6 7 8 9 10 Next >>