Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:151-18-8 (BAPN)
 130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lathyrogens decrease collagen and elastin cross-linking by inhibiting lysine oxidase. The lathyrogens isoniazid and semicarbazide decrease liver pyridoxal phosphate and are teratogenic; all their effects are reversed by pyridoxal. beta-Aminopropionitrile, another lathyrogen, does not affect liver pyridoxal phosphate, and its lathyrogenic and teratogenic effects are not reversed by pyridoxal. Time courses of these effects differ greatly, suggesting enzyme inhibition by different mechanisms.
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PMID:The inhibition of protein-lysine 6-oxidase by various lathyrogens. Evidence for two different mechanisms. 408 35

1. Na(2) (35)SO(4), [1-(14)C]glucosamine and [1-(14)C]acetate were used as precursors of the sulphated glycosaminoglycans to study the biochemical effect of beta-aminopropionitrile in chick embryos. The incorporation of all three precursors was decreased in the treated embryos between days 7 and 10 of embryonic development. No inhibition of incorporation of these precursors occurred between days 16 and 20 of embryonic development at the dosages of beta-aminopropionitrile used. 2. beta-Aminopropionitrile treatment also decreased the amount of N-acetylhexosamines in the chick embryo and decreased the percentage of the hexosamine esterified by nucleotides. Respiration was decreased by homogenates prepared from treated embryos. Likewise, UDP-xylosyl- and UDP-galactosyl-transferase activities were decreased in treated embryos and cartilage from embryos and growing chicks. 3. The data suggest that beta-aminopropionitrile, in addition to the known lathyrogenic activity, either is or gives rise to a potent metabolic poison that interferes with basic cellular metabolism. The results are consistent with a decreased rate of ATP generation as an explanation for the decrease in glycosaminoglycan synthesis.
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PMID:Alterations in glycosaminoglycan metabolism in beta-aminopropionitrile-treated chick embryos. 427 79

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 (beta APN), an agent that prevents collagen accumulation in tissues, was evaluated for its ability to prevent excess collagen formation in bleomycin-induced pulmonary fibrosis in the hamster. Two groups of animals received a single endotracheal dose of bleomycin; one of these was injected with beta APN twice daily for 30 days. A third group received endotracheal saline and a fourth group received saline and beta APN. After 30 days, we measured pressure-volume curves of saline-filled lungs, collagen content, and degree of fibrosis. Endotracheal bleomycin increased collagen content, decreased lung volume, and produced fibrosis and a mortality rate of 51%. The administration of beta APN to bleomycin-treated animals prevented excess collagen accumulation and diminished total protein, reversed volume diminution, produced less fibrosis, and improved the mortality rate to 24%; beta APN alone had no effect on lung mechanics or collagen content. The biochemical, functional, and structural features of bleomycin-induced lung fibrosis are amenable to control with beta APN.
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PMID:beta-Aminopropionitrile prevents bleomycin-induced pulmonary fibrosis in the hamster. 617 60

In the rat the administration of lathyrogenic toxic agents at low doses over prolonged periods of time caused simultaneous alterations in aortic and cutaneous tissues. BAPN caused an increase in soluble collagen in the skin, but in aorta there was no increase in neutral salt soluble collagen, but an increase in the amount that could be solubilized with pepsin. Type III collagen was found to represent 7% in the control aorta samples and this level was not affected by BAPN. In skin Type III accounts for 11% of the extractable collagen in controls and 14% in lathyritic animals. Biochemical changes observed in this study show evidence for collagenous lesions by increases in solubility in both skin and aorta but in neither tissue was the percentage of Type III altered by lathyrism.
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PMID:Lathyrism: aortic and cutaneous collagen in the rat. 621 55

The administration of lathyrogenic agents (BAPN) at weak and prolonged doses (9 weeks, 1 g/kg/day) induced in the rat simultaneous alterations of aortic and cutaneous connective tissues comparable to the modifications observed during ageing in man. The lathyrogens produced this effect of inhibiting lysine-oxydase, the enzyme responsible for cross-linking collagen and elastin which leads to an increase in extractable collagen in the tissues. But BAPN did not appear to affect synthesis of collagen either in amount or in types I and III collagen ratio.
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PMID:[Lathyrism and collagens I and III (author's transl)]. 628 14

BAPN (0.1 mg/day) was injected into chick embryos for 4 days starting on the 7th day of incubation. On the 11th day, the embryos were administered either 3H-proline or 3H-lysine. 36 h later, the incorporation of each isotope by the periosteal osteogenic cells as well as into bone matrix was investigated by autoradiography. The incorporation of the two isotopes into whole bones was assessed by liquid scintillation counting. 3H-proline incorporation into the cellular or matrical compartments was unaffected by treatment. As compared to the controls, 3H-lysine label in BAPN-treated embryonic bones was significantly higher in the cellular compartment but was reduced over the bone matrix. The data provide the first direct morphological evidence that BAPN probably induces certain changes in the maturation of collagen involving lysyl residues which result in an inhibition of cross-linkage formation in collagen.
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PMID:Autoradiographic and liquid scintillation assessment of beta-amino-propionitrile-induced inhibition of collagen maturation using 3H-proline and 3H-lysine. 640 23

Neonatal pig and rat aortas were studied for their ability to synthesize elastin in an in vitro situation. Smooth muscle cells from the rat aorta produced excellent multilayered cultures and produced soluble elastin (tropoelastin), insoluble elastin, and small amounts of collagen. BAPN proved to be toxic to these cells, adversely affecting the level of extracellular protein production. Tissue minces from pig aorta continued to synthesize elastin for two hours after removal. However, a 24 hour study indicated that elastin synthesis had almost completely shut down and that collagen synthesis continued in an apparently normal fashion. It is concluded that in vitro elastin synthesis is an extremely sensitive process easily altered by culture conditions and the addition of extraneous substances such as BAPN, and also highly influenced by the past history of the smooth muscle cells involved.
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PMID:In vitro studies of elastin metabolism. 645 49

BAPN (beta-aminopropionitrile), a known inhibitor of collagen cross-linking, was instilled topically three times a day for 11 to 14 days in the eyes of rabbits after they had sustained central corneal wounds. In eight of nine rabbits, corneal wound tensile strength was significantly less in BAPN-treated eyes as compared to controls. This finding has important implications in all areas of ocular surgery and injury for control of collagen maturation and its complications in healing.
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PMID:Effect of beta-aminopropionitrile (BAPN) on corneal wound strength. 647 92

beta-Aminopropionitrile as free base (BAPN) was applied onto the incised or intact skin of rats at the dose of 5, 20, 100, and 200 microliters for 9 days, twice daily. Breaking strength of the skin wound or intact skin was significantly reduced at doses of 20 microliters and higher; body weight growth was significantly retarded at the two highest dosages. It is concluded that at a given dose (20 microliters) collagen polymerization (evaluated by reduced breaking strength and increased extractability of collagen) was specifically inhibited by BAPN. Furthermore, no evidence of topical or general toxic effects were observed, as reflected in histology, body weight growth, and behavior of the rats. Acute LD50 of BAPN base and fumarate, administered either ip or topically, was determined in mice. While BAPN base in ip administration shows LD50 of 1.15 g/kg, in cutaneous application it is more than 12.8 g/kg. It is suggested that topically applied BAPN base is percutaneously absorbed and affects collagen polymerization in the skin and adjacent tissues.
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PMID:Healing of skin incision wounds treated with topically applied BAPN free base in the rat. 661 24


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