Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta-Aminopropionitrile, a specific inhibitor of lysyl oxidase prevented the rise in blood pressure induced by deoxycorticosterone-salt in rats. In addition, after the onset of hypertension, administration of beta-aminopropionitrile lowered the blood pressure. Concomitant with the lowering of blood pressure, there was a reduction in the more highly crosslinked form of vascular collagen. These findings would indicate that increases in vascular connective tissue are not only sequelae of hypertension, but may also contribute to the maintenance of elevated blood pressure.
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PMID:Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile. 26 88

beta-Aminopropionitrile (BAPN) administered to rats has caused exostosis formation at sites of muscle attachment and also caused delay in the healing of soft tissue wounds and of bone fractures. Since phenytoin sodium has an opposite effect on wound healing, bone fractures, and the tensile strength of connective tissues, an experiment was performed to determine whether or not BAPN could produce periosteal exostoses in the presence of phenytoin. Rats that were given both BAPN and phenytoin produced similar exostoses as rats that were given BAPN alone. This indicates that phenytoin does not prevent inhibition of lysyl oxidase by BAPN, does not promote increased tensile strength of connective tissues in the presence of BAPN, and does not facilitate the detoxification of BAPN. Further, no evidence for an increased cellular response with phenytoin was observed. The mechanism by which phenytoin promotes wound healing is still unknown.
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PMID:Phenytoin inhibition: failure to inhibit periosteal responses to lathyrogen. 57 90

beta-Aminopropionitrile (BAPN) is an inhibitor of the lysyl oxidase required for cross-link formation in collagen maturation. The efficacy of BAPN, alone or in association with the anti-schistosomal drug, praziquantel (PZQ), was primarily assessed by measuring the reduction in liver and intestinal egg loads in murine schistosomiasis mansoni. Depending on the treatment group (PZQ, BAPN, BAPN + PZQ), organ-specific effects were observed using microscope image analysis. Most notable was the relatively small size of granulomas in the livers of BAPN-treated mice, which contrasted with the relatively large size and irregular shape of the granulomas in the intestinal tissues of these mice. Mice treated with the combination of BAPN and PZQ had decreased liver and spleen weights, and a significant reduction in the number of eggs trapped in both the liver (86%) and the intestine (99.1%), compared with untreated mice and those given PZQ alone. The lowest number of living eggs/g of tissue in both the liver and intestine was recorded in the combined BAPN + PZQ-treated group. These results suggest that the concurren treatment of infected mice with PZQ and BAPN enhances the release of eggs trapped in the intestine and also results in a significant reduction of liver egg load. The mechanism by which BAPN reduces the number of liver granulomas in PZQ-treated mice is currently being investigated.
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PMID:Experimental schistosomiasis mansoni: modulation of granulomas by inhibition of collagen cross-link formation. Preliminary report. 130 5

The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with beta-aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries - to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents.
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PMID:Spontaneous rupture of the internal elastic lamina in the rat: the manifestation of a genetically determined factor which may be linked to vascular fragility. 257 18

The effect of chronic lathyrism on the mandible of the rat was studied. Exostoses, thinning and discoloration of the cortical plates, intraosseous bleeding and hemorrhagic cyst were observed after six weeks of administration of beta-aminoproprionitrile fumarate. The exostoses consisted of homogeneous cellular fibrous tissue containing osteoid, hyalin-like material and abundant ground substance. The cysts were filled with erythrocytes and lined by spindle-shaped fibroblasts, collagen fibers or osteoblast-like cells. Between the cysts, bands and sheets of dense and cellular connective tissue presenting foci of hemorrhage, osteoid and metaplastic cartilage were found. Numerous mast cells were demonstrated with alcian and toluidine blue in the hematopoietic bone marrow, cancellous bone and around the capillary network surrounding the exostoses and cysts. Exostoses have already been studied and explained by the action of BAPN (lysyl oxidase). Hemorrhagic cysts could be explained by histamine release from the mast cells (hypervascularity, hyperemia, increased permeability, rupture and progressive confluence of these small hemorrhagic cysts). Histopathology of the experimental cysts had some points in common with the human aneurysmal bone cyst. Could the pathogenic mechanisms be similar for both lesions?
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PMID:Experimental lathyrism: exostoses and aneurysmal-like bone cysts of the mandible in the rat. 343 20

beta-Aminopropionitrile (BAPN) is a potent irreversible inhibitor of lysyl oxidase, the enzyme which initiates cross-linkage formation in elastin and collagen. The initial interaction of BAPN with aortic lysyl oxidase is competitive with elastin or alkyl amine substrates. Irreversible inhibition develops in a time- and temperature-dependent fashion upon incubation of enzyme with BAPN in the absence of substrate with a limiting inactivation rate constant of 0.16 min-1 and a KI of 6 microM at 37 degrees C. The labeled carbons of [1,2-14C]BAPN and [3-14C]BAPN covalently bind to the enzyme to equivalent extents and in parallel with the development of inactivation, negating the possibility that the nitrile moiety is eliminated from BAPN by enzymatic action. The copper content of the enzyme is not significantly altered upon interaction with BAPN. The extent of labeling by [14C]BAPN is reduced by prior treatment of the enzyme with carbonyl-modifying reagents, suggesting the possibility of enzyme-inhibitor Schiff base formation. However, BAPN is not processed to a free aldehyde product upon incubation with lysyl oxidase. A mechanism of inhibition is postulated which involves the formation of a covalent bond between an enzyme nucleophile and a ketenimine formed from BAPN by enzyme-assisted beta-proton abstraction.
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PMID:Reaction of aortic lysyl oxidase with beta-aminopropionitrile. 613 92

beta-Aminopropionitrile, a lysyl oxidase and collagen cross-linkage inhibitor, resulted in a 0.90 diopter or 20% enhancement of radial keratotomy in rabbits.
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PMID:Enhancement of radial keratotomy by chemical inhibition of collagen cross-linkages: a preliminary report. 666 Jul 29

beta-Aminopropionitrile (beta-APN), a lathyrogen, alters the physical characteristics of fibrous scar tissue and as such may have potential clinical use in treatment of injured spinal cord and peripheral nerve by reducing the physical barrier to axon regeneration. For beta-APN to exert its lathyrogenic effect, it must permeate the injury site and gain access to the developing collagenous scar. To investigate the diffusion characteristics, beta-[14C]APN solution was applied as an immersion bath to rat sciatic nerve using both in vivo and in vitro preparations for intervals of 15 to 90 min. The four experimental groups studied were (a) intact nerve, (b) hemisected nerve, (c) nerve with epineurium removed, and (d) nerve with both epineurium and perineurium removed. The isotope labeling index determined by autoradiography and scintillation counting indicated the perineurium as the primary barrier to significant diffusion of beta-APN in normal nerve. When perineurium was incised or removed, beta-APN entered the endoneurial matrix. beta-APN concentration in the epineurium and perineurium increased with increasing bathing time in vitro; but it decreased markedly after 15 min of in vivo bathing. These findings indicate that topical application of beta-APN to injured peripheral nerve would be a successful method of exposing fibrogenic intraneural tissue to the inhibitory effect on lysyl oxidase enzymes. Continuous application, however, will be necessary because of the rapid beta-APN removal documented in the vivo preparation.
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PMID:Diffusion characteristics of beta-aminopropionitrile in peripheral nerve. 682 64

We have measured the dynamics of extracellular matrix consolidation and strengthening by human dermal fibroblasts in hydrated collagen gels. Constraining matrix consolidation between two porous polyethylene posts held rigidly apart set up the mechanical stress which led to the formation of uniaxially oriented fibroblast-populated collagen matrices with a histology resembling a ligament. We measured the mechanical stiffness and tensile strength of these ligament equivalents (LEs) as a function of age at biweekly intervals up to 12 weeks in culture using a mechanical spectrometer customized for performing experiments under physiologic conditions. The LE load-strain curve changed as a function of LE age, increasing in stiffness and exhibiting less plastic-like behavior. At 12 weeks, LEs had acquired up to 30 times the breaking strength of 1-week-old LEs. Matrix strengthening occurred primarily through the formation of BAPN-sensitive, lysyl oxidase catalyzed crosslinks. Sulfated glycosaminoglycan (GAG) content increased monotonically with LE age, reaching levels that are characteristic of ligaments. Cells in the LEs actively incorporated [3H]proline and [35S]sulfate into the extracellular matrix. Over the first three weeks, DNA content increased rapidly but thereafter remained constant. This data represent the first documentation of strengthening kinetics for cell-assembled biopolymer gels and the results suggest that this LE tissue may be a valuable model for studying the cellular processes responsible for tissue growth, repair, and remodeling.
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PMID:Mechanisms and dynamics of mechanical strengthening in ligament-equivalent fibroblast-populated collagen matrices. 832 28

beta-Aminopropionitrile (beta APN), inhibits the activity of lysyl oxidase, an important enzyme for the post-translational formation of inter- and intramolecular covalent cross-linking between the connective tissue proteins, collagen and elastin. We became interested in the possible use of this compound as a therapeutic agent in the so-called human collagen diseases. beta APN's action mechanism is known, but its pharmacokinetics in rabbits have not yet been determined. The present study defined the kinetic parameters of beta APN in rabbits, after oral or intravenous (iv) administration. The HPLC technique was recently modified using OPA (ortho-phthalaldehyde) as the derivative agent. beta APN plasma concentration vs time following the iv administration of 200 mg/kg was best described by the biexponential equation C = 92.43.e(-0.0728 t) + 61.78.e(-0.0088 t) (t1/2 beta = 78.73 +/- 5.19 min; Vc = 1.29 +/- 0.04 L.kg-1). After oral administration, beta APN followed a zero-order absorption pattern (Ko = 3.02 +/- 0.34 mg.kg-1.min-1), which means that the beta APN reached the blood very quickly.
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PMID:Pharmacokinetic analysis of beta-aminopropionitrile in rabbits. 872 Dec 91


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