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At least 631 records · Page 35Linked to original sources
PubMed1979

Biosynthesis of basement membrane matrix by isolated rat renal glomeruli.

The incorporation of radioactive precursors into the extracellular basement membrane matrix has been investigated in a purified preparation of isolated rat kidney glomeruli. Using deoxycholate extraction of isolated glomeruli which were incubated with radioactively labeled amino acids and carbohydrates, as an assay system for the measurement of incorporation of basement membrane precursors into intact deoxycholate insoluble basement membrane material, we demonstrated the in vitro biosynthesis of this structure. The assay system minimized the possibility of contamination of the isolated labeled basement membrane with labeled cell membrane fragments which may occur with the standard isolation procedures involving sonication and centrifugation. A linear incorporation of labeled proline, lysine, glycine, glucosamine, and galactose into glomerular basement membrane was shown. Basement membrane synthesis was inhibited by metabolic poisons and protein synthesis inhibitors as well as by inhibitors of collagen synthesis, but not by colchicine, an inhibitor of collagen secretion. Rhe appearance of 14C-hydroxyproline in the basement membrane matrix was negligible during the first 4 hours of incubation and rose only to 1% of the total proline counts thereafter. The results are consistent with the characterization of glomerular basement membrane synthesis and deposition as a two component system comprising a rapidly synthesized and deposited noncollagenous glycoprotein component(s) and a collagenous component which is only deposited after a delay of 4 to 6 hours.

Aminopropionitrile↗
PubMed1972

Collagen heterogeneity within different growth regions of long bones of rachitic and non-rachitic chicks.

The different anatomical regions involved in osteogenesis in the chick long bone have been examined for heterogeneities in collagen structure that might relate to the mechanism of ossification. Experimentally induced lathyrism was employed to enhance collagen solubility, and vitamin D deficiency to allow accumulation of osteoid, the precursor of bone matrix. The extractable lathyritic collagens of the cartilaginous and osseous regions of growing long bones from rachitic and non-rachitic chicks were examined for alpha-chain type and amino acid composition. In both groups of animals the growth plate and cartilaginous regions of the epiphysis gave collagen molecules of the constitution [alpha1(II)](3), whereas the ossifying regions contained [alpha1(I)](2) alpha2. The degree of hydroxylation of the lysine moieties was increased by approximately 50% in the alpha1(I)-chain and alpha2-chain of rachitic bone collagen. Since uncalcified osteoid is greatly enriched in rachitic bone, it is concluded that the collagen of osteoid has the configuration [alpha1(I)](2) alpha2, similar to that of bone matrix, but has an elevated hydroxylysine content. The possible relationship of this difference to the mechanism of calcification is discussed.

Amino Acids↗
PubMed1997

Spfkh1 encodes a transcription factor implicated in gut formation during sea urchin development.

A member of the forkhead class of transcription factors from sea urchins (Spfkh1) that is expressed specifically in the endoderm of developing embryos has been identified. Spfkh1 was expressed transiently in the embryo, with peak levels of messenger ribonucleic acid (mRNA) accumulating at the time endoderm invaginated into the interior of the embryo. Expression was limited to the invaginating endoderm in the early gastrula, then became further restricted to the base of the invaginating gut at the mid-gastrula stage. Expression diminished by the end of gastrulation. This expression pattern indicates that Spfkh1 mRNA accumulates in endodermal cells as they invaginate, but disappears rapidly in endodermal cells that undergo convergent extension. Treatment of embryos during cleavage stages with lithium or phorbol esters caused an increase in Spfkh1 mRNA accumulation and expanded the domain of expression of Spfkh1, suggesting that signaling through the inositol-tris-phosphate protein kinase C (IP3-PKC) signaling pathway is upstream of Spfkh1 expression. The expression pattern of Spfkh1 suggests that it is centrally involved in specification and/or differentiation of the gut. Disruption of the extracellular matrix (ECM) prevents formation of the gut, but does not inhibit initiation of Spfkh1 expression. Embryos arrested prior to gastrulation continued to express Spfkh1 well past the time it was down-regulated in normal embryos, suggesting the ECM or cell movement is required for the decrease in Spfkh1 mRNA during gastrulation.

Amino Acid Sequence↗
PubMed2002

Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO).

Tresperimus (Cellimis), a new immunosuppressive agent, is mainly eliminated in the rat through metabolism, in which the oxidative deamination of the primary amine of the drug plays a major role. We have previously demonstrated in vivo the significant involvement of semicarbazide-sensitive amine oxidase (SSAO) in this reaction. Rat aorta, a tissue with one of the highest specific SSAO activities, was tested as a new in vitro model to elucidate tresperimus metabolism, using a combination of liquid chromatography/mass spectrometry (LC/MS) and high-performance liquid chromatography (HPLC) analyses. The metabolites resulting from the main metabolic pathway of the drug were formed in rat aorta homogenates. The use of various SSAO, lysyl oxidase and monoamine oxidase inhibitors confirmed that SSAO is predominantly involved in the main site of tresperimus metabolism but also in every metabolic pathway of the drug, including deamination of tresperimus metabolites M3 (desaminopropyl derivative of tresperimus) and M6 (guanidinohexylamine). A microsomal fraction of the rat aorta was used to characterize tresperimus deamination. The moderate affinity of membrane-bound SSAO for tresperimus, with a Km value of 66 microM, was counterbalanced by a catalytic efficiency superior to that of certain physiological substrates of SSAO, such as methylamine. The rat aorta provided an interesting model with which to study tresperimus metabolism, highlighting the important role that SSAO could play as a phase I oxidative enzyme in the metabolism of certain exogenous amines at the vascular level.

Amine Oxidase (Copper-Containing)↗
PubMed2005

Drosophila lysyl oxidases Dmloxl-1 and Dmloxl-2 are differentially expressed and the active DmLOXL-1 influences gene expression and development.

Mammalian lysyl oxidase (LOX) is essential for the catalysis of lysyl-derived cross-links in fibrillar collagens and elastin in the extracellular matrix and has also been implicated in cell motility, differentiation, and tumor cell invasion. The active LOX has been shown to translocate to the nuclei of smooth muscle cells and regulate chromatin structure and transcription. It is difficult to interpret the role of the LOX protein as it is co-expressed with other members of the LOX amine oxidase family in most mammalian cells. To investigate the function of the LOX proteins, we have characterized the Drosophila lysyl oxidases Dmloxl-1 and Dmloxl-2. We present the gene, domain structure, and expression pattern of Dmloxl-1 and Dmloxl-2 during development. In early development, only Dmloxl-1 was expressed, which allowed functional studies. We have expressed Dmloxl-1 in S2 cells and determined that it is a catalytically active enzyme, inhibited by beta-amino-proprionitrile (BAPN), a specific LOX inhibitor. We localized DmLOXL-1 in the nuclei in embryos and in adult salivary gland cells in the nuclei, cytoplasm, and cell surface, using immunostaining and a DmLOXL-1 antibody. To address the biological function of Dmloxl-1, we raised larvae under BAPN inhibitory conditions and over-expressed Dmloxl-1 in transgenic Drosophila. DmLOXL-1 inhibition resulted in developmental delay and a shift in sex ratio; over-expression in the w(m4) variegating strain increased drosopterin production, demonstrating euchromatinization. Our previous data on the transcriptional down-regulation of seven ribosomal genes and the glue gene under inhibitory conditions and the current results collectively support a nuclear role for Dmloxl-1 in euchromatinization and gene regulation.

Active Transport, Cell Nucleus↗
PubMed1994

Reduction in tissue egg load and maintenance of resistance to challenge in mice infected with Schistosoma mansoni, following combined treatment with praziquantel and an antifibrotic agent.

Antifibrotic therapy with beta-aminoproprionitrile (BAPN), when combined with praziquantel (PZQ) treatment of mice infected with Schistosoma mansoni, led to a marked change in the temporal pattern of parasite egg excretion. The rate of egg excretion was higher and terminated sooner and the tissue egg load was smaller in mice treated with BAPN and PZQ than in mice treated with PZQ alone. Some of the mice that received the combined treatment were challenged 2 or 5 weeks after PZQ treatment; they retained a high level of resistance to challenge, similar to that observed in untreated, infected mice. In contrast, mice given only PZQ were as susceptible to challenge as the uninfected control mice. The activity of peritoneal macrophages, as measured by their production of hydrogen peroxide, nitric oxide and tumour necrosis factor alpha in vitro, was only elevated in cells obtained from untreated, infected mice. These results demonstrate that modulation of granuloma formation by combined antifibrotic/PZQ therapy significantly changes the dynamics of egg granuloma formation and attenuates the host's resistance to challenge infection.

Aminopropionitrile↗
PubMed1997

Effect of beta-aminoproprionitrile on eggshell formation.

1. Eggshells are bioceramic-biopolymer composites made by a cell-mediated deposition of an extracellular matrix which drives the organisation of the inorganic phase. Ultrastructurally, eggshells are composed of shell membranes, mammillary knobs, palisade, and cuticle. Shell membranes are two nets of type X collagen-containing fibrils. On to these membranes, the mammillary knobs, that is, the crystal nucleation sites, are deposited. Type X collagen is highly cross-linked and insoluble. 2. In order to evaluate the role of type X collagen cross-linking on eggshell formation, hens were injected with different doses of beta-aminoproprionitrile, which specifically interferes with cross-link formation. 3. Changes in egg size and shape were observed. Scanning electron micrographs analysis of these eggs demonstrated marked changes in crystal growth and shell membrane structure and arrangement. A dot-blot analysis, using a monoclonal antibody against chicken type X collagen, shows a dose-dependent increase in shell membrane collagen extractability. 4. It is concluded that the formation of beta-aminoproprionitrile-sensitive cross-links among the type X collagen molecules of the shell membranes play an essential role in normal eggshell formation.

Aminopropionitrile↗
PubMed1985

In vivo and in vitro release of cyanide from neurotoxic aminonitriles.

Cyanide release from neurotoxic aminonitriles was measured following in vitro incubation with both microsomes and liver slices. Investigation of cyanide released as urinary thiocyanate following ip aminonitrile administration to rats was also measured. The yield of cyanide in the in vivo study, as measured by the mole percent of administered dose, was greatest from dimethylaminonitrile (DMAA), followed by trimethylaminopropionitrile (TMAPN), dimethylaminopropionitrile (DMAPN), 3,3'-iminodipropionitrile (IDPN), dimethylaminobutyronitrile (DMABN), and monomethylaminopropionitrile (MMAPN). Urinary excretion of thiocyanate accounted for 48.9% of the administered DMAA, 11.6% of TMAPN, 8.0% of DMAPN, 6.8% of IDPN, 3.1% of DMABN, and 1.8% of MMAPN. Incubation of aminonitriles and related compounds with microsomes or liver slices from rats yielded measurable quantities of cyanide from all the compounds tested except for DMABN, TMABN, and succiononitrile. Quantitative evaluation of the yield of formaldehyde by demethylation following microsomal incubation was also determined. The signs of acute toxicity in rats after ip administration of KCN were similar only to those in rats administered DMAA.

Aminopropionitrile↗
PubMed1985

Evaluation of the inhibition of glycolytic enzymes by the neurotoxicant dimethylaminopropionitrile.

The neurotoxic aminonitrile dimethylaminopropionitrile (DMAPN) inhibits the crystalline glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fructose-6-phosphate kinase (phosphofructokinase, PFK). Preincubation of GAPDH with the aminonitrile enhances the inhibition, indicating that the inhibition is irreversible. The overall bimolecular rate constant ki was determined to be 2.42 +/- 0.21 M-1 min-1. Dithiothreitol (DTT) partially protected the enzyme from inhibition. PFK is also inhibited by DMAPN, but the inhibition is reversible and noncompetitive with a Kl, of 2.79 X 10(-2) M. DMAPN does not inhibit lactate dehydrogenase (LDH), nor is GAPDH or PFK inhibited by 3,3'-iminodipropionitrile (IDPN).

Aminopropionitrile↗
PubMed1991

Studies on the mechanism of urotoxic effects of N,N'-dimethylaminopropionitrile in rats and mice. 1. Biochemical and morphologic characterization of the injury and its relationship to metabolism.

N,N'-Dimethylaminopropionitrile (DMAPN), a major component of the NIAX catalyst ESN, is known to cause urinary bladder dysfunction in exposed workers. In order to investigate the mechanism of DMAPN toxicity, we carried out time-course (0-72 h) and dose-response (175-700 mg/kg) studies on the effects of DMAPN in rats and mice. Treated animals exhibited several signs of toxicity including loss of body weight, reduced water consumption, and bladder urine retention, as well as bladder injury. DMAPN-induced bladder injury was characterized by distended bladders with marked diffuse submucosal and subserosal edema, petechial hemorrhage, and multifocal perivascular inflammatory infiltrates. The qualitative and quantitative analysis of urine indicated hypoosmolality, aciduria, hematuria, proteinuria, and oliguria. Elevated levels of creatinine and urea levels in plasma were indicative of renal dysfunction. Within hours following DMAPN administration, the animals exhibited a significant increase in urinary retention that resolved between 60 and 72 h. Rats excreted about 44% of the administered DMAPN dose unchanged in the urine, while mice excreted only about 6% of the dose. Commercially available DMAPN metabolites, administered by gavage, produced toxic effects less adverse than DMAPN. The biochemical effects of DMAPN included depletion of glutathione and increased lipid peroxidation in target organs, including urinary bladder and kidney. These studies indicate that there are species differences in DMAPN toxicity. The differences may be due to differences in the formation of reactive metabolic intermediates of DMAPN.

Aminopropionitrile↗
PubMed1960

Electron microscope study of the lathyritic rat aorta.

Six weanling rats were fed a diet containing 0.4 per cent BAPN fumarate and sacrificed after 5 to 33 days on the diet. The ascending aortae were fixed with OsO(4), embedded in methacrylate and araldite, sectioned, stained with lead hydroxide, and examined with the electron microscope. The descending thoracic aortae were examined by light microscopy. Compared with pair-fed controls, the experimentals showed definite changes which became more marked as the disease progressed. The wall became thicker with wider interlaminar spaces, radial orientation of the smooth muscle cells, progressive loss of desmosomes, and progressive increase in a dense, finely stippled material that coated the edges of the elastic laminae and extended outwards between the muscle cells and separated the ends of these cells from the laminae. This stippled material occurred at the same sites as the increase in PAS-positive and azan-positive material seen with the light microscope. There was an increase in subendothelial and interlaminar collagen, and electron microscopy clearly showed that the cells were smooth muscle and not fibroblasts. The possible bearing of the morphological changes on the formation of aortic aneurysms is discussed.

Aminopropionitrile↗
PubMed1974

Lathyrism: a review.

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Abnormalities, Drug-Induced↗
PubMed2002

Collagen fibrillogenesis by chondrocytes in alginate.

Collagen is the primary structural component in connective tissue. The poor mechanical properties of most cell-seeded cartilage grafts used for cartilage repair can be attributed to the low level of collagen synthesized compared with native cartilage. In this study, the synthesis and assembly of collagen by chondrocytes in hydrogels were investigated, with particular attention paid to the role of cross-link formation in this process. Primary bovine chondrocytes were seeded in alginate and collagen synthesis was assessed in the presence and absence of beta-aminopropronitrile (BAPN), a potent inhibitor of the enzyme lysyl oxidase and collagen cross-link formation. Cultures on days 21, 35, and 49 were evaluated by stereology, biochemistry, and real-time reverse transcriptase-polymerase chain reaction. All measures of collagen synthesis (except hydroxyproline) significantly increased in the presence of 0.25 mM BAPN. By 35 days of culture, the average collagen fibril diameter was 62 +/- 10 nm in control cultures and 109 +/- 20 nm with BAPN supplementation. The collagen volume density increased from 5 +/- 3% in control cultures to 17 +/- 1% in the presence of BAPN. Likewise, the expression of cartilage-specific collagens (type II and XI) and aggrecan increased significantly as a result of BAPN culture. These findings demonstrate the prominent role of collagen cross-linking in collagen fibrillogenesis and suggest approaches by which collagen synthesis and assembly could be controlled in tissue-engineered constructs.

Alginates↗