Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Samples from the ascending aortae from two calves affected by bovine Marfan syndrome were subjected to biochemical analyses of the connective tissue and were compared to age-matched controls. Elastin was extracted from the aortic samples with 5 M guanidine-HCl, bacterial collagenase digestion, and dithiothreitol reduction. Amino acid analysis revealed that desmosine and isodesmosine levels were the same in Marfan calves as in control animals. Gravimetric measurements of elastin, amino acid composition, soluble protein, and uronic acid values also showed no significant difference between Marfan and control tissue. In contrast to elastin, collagen in aortae of Marfan calves was significantly higher than the mean of several controls. These findings, along with other observations of this animal model, support the conclusion that the microscopic and biochemical lesions of aortic elastin in bovine Marfan syndrome likely result from defective microfibrillar metabolism. Absence of cystic medial necrosis in bovine Marfan aortae may explain normal elastin content in the animal model.
Exp Mol Pathol 1992 Oct
PMID:Normal elastin content of aorta in bovine Marfan syndrome. 142 58

Invasive pulmonary aspergillosis, usually caused by Aspergillus fumigatus, is a life-threatening condition of immunosuppressed patients. We have created a mutant strain of this fungus that lacks an extracellular alkaline protease (AFAlp). This was accomplished by transformation of A. fumigatus with a plasmid containing a selectable marker for hygromycin B resistance, and a 504 bp segment of the AFAlp gene, obtained by polymerase-chain-reaction-based amplification of A. fumigatus genomic DNA. Approximately 25% of transformants resulted from disruption of the AFAlp gene. SDS-polyacrylamide gel electrophoresis of proteins from the culture filtrate of a strain carrying the AFAlp gene disruption showed that it lacked a major protein of 33 kDa. Furthermore, in contrast to the culture filtrate from wild-type cells, the mutant had undetectable activity on azocollagen and elastin-Congo red, over a broad pH range. This shows that AFAlp accounts for most, if not all, of the extracellular elastinolytic activity of A. fumigatus, and that the mutant strain will be useful in assessing the role of AFAlp in pathogenicity.
Mol Microbiol 1992 Jun
PMID:An Aspergillus fumigatus alkaline protease mutant constructed by gene disruption is deficient in extracellular elastase activity. 149 93

Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable degree of molecular mimicry to the extracellular matrix protein elastin. It contains both repetitive motifs PGVGV and VGVAPG. Immunofluorescence using a monoclonal antibody against VGVAPG confirmed that this peptide is expressed on sporozoites as predicted. The presence of VGVAPG is particularly interesting since this is the ligand for elastin receptors on a range of cell types, including macrophages/monocytes which are a major class of host target cells. It is proposed that this antigen represents the ligand whereby T. annulata recognises its host cells.
Mol Biochem Parasitol 1992 Jul
PMID:Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen. 150 30

Full elastolytic activity in Pseudomonas aeruginosa is a result of the combined activities of elastase, alkaline proteinase, and the lasA gene product, LasA. The results of this study demonstrate that an active fragment of the LasA protein which is isolated from the culture supernatant fraction is capable of degrading elastin in the absence of elastase, thus showing that LasA is a second elastase produced by this organism. In addition, it is shown that LasA-mediated enhancement of elastolysis results from the separate activities of LasA and elastase upon elastin. The LasA protein does not affect the secretion or activation of a proelastase as previously proposed in other studies. Furthermore, LasA has specific proteolytic capability, as demonstrated by its ability to cleave beta-casein. Preliminary analysis of beta-casein cleavage in the presence of various protease inhibitors suggests that LasA may be classified as a modified serine protease.
Mol Microbiol 1992 May
PMID:Further studies on Pseudomonas aeruginosa LasA: analysis of specificity. 158 15

Lysyl oxidase catalyzes the oxidation of peptidyl lysine to alpha-aminoadipic-delta-semialdehyde, the precursor to the covalent crosslinkages that stabilize fibers of elastin and collagen. This enzyme contains both copper and a carbonyl cofactor consistent with an o-quinone. The proposed mechanism of action is derived from available kinetic and chemical data and also can account for mechanism-based inhibition of the enzyme by specific monoamines and diamines. Recent evidence for biosynthetic precursors and for the regulation of lysyl oxidase in fibrotic and malignant diseases is discussed.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Properties and function of lysyl oxidase. 191 Aug 5

Animals chronically exposed to hypoxia develop characteristic structural changes in the pulmonary arterial vasculature including cell hypertrophy, hyperplasia, and increased deposition of extracellular matrix proteins. The medial smooth muscle cells' (SMC) increase in tropoelastin mRNA expression and elastin deposition as determined by in situ hybridization and histologic examination appears to contribute significantly to this increase in matrix protein accumulation. The primary stimulus for the increased tropoelastin production, which persists in vitro, is unknown but mechanical forces and hypoxia seem to play a role. In order to determine the direct effects of hypoxia on tropoelastin production by pulmonary artery SMC, cultured neonatal bovine pulmonary artery SMC were exposed to 3%, 10%, and 21% O2 concentrations for 48, 72, and 120 h and soluble tropoelastin was measured by direct immunoassay. Tropoelastin mRNA levels were also determined by Northern and slot blot analysis after 48 h of incubation under hypoxic conditions. SMC cultured in 3% and 10% O2 for 120 h showed dose-dependent decreases (11-fold and 2-fold, respectively) in measured tropoelastin levels compared with SMC cultured in 21% O2 conditions. This decrease was not due to cell damage or accumulation of toxic metabolites while under hypoxic conditions nor to a change in tropoelastin partitioning between the cell and media. Tropoelastin mRNA levels were also decreased under hypoxic conditions. Secreted, cell layer, and total protein synthesis determined by L-[3H]leucine incorporation again showed a dose-dependent decrease under hypoxic conditions but not to the same extent as tropoelastin production.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Nov
PMID:Hypoxia-induced inhibition of tropoelastin synthesis by neonatal calf pulmonary artery smooth muscle cells. 171 37

Gene expression for tropoelastin, the proprotein for elastin, was examined in the rat lung from 17 days of gestation (pseudoglandular stage) to adulthood by in situ hybridization using a rat-specific 35S-radiolabeled riboprobe. The tropoelastin message was present in vascular and airway smooth muscle, endothelial, septal interstitial, alveolar wall, and mesothelial cells but not in epithelial cells. With alveolar septal formation, the message in the interstitium increased progressively from 17 days of gestation, reaching a peak at 7 to 11 days postnatal. The signal in the arterial walls, in contrast, peaked between 19 days of gestation to 1 day postnatal and thereafter declined first from the outer media. The signal in general declined significantly by 21 days postnatal, and elastogenesis was virtually absent in the adult. These results support the idea that tropoelastin gene expression in the interstitium is closely associated with the centripetal progression of alveolarization, and the early postnatal decrease of tropoelastin expression in blood vessels corresponds with the sudden postnatal changes in the pulmonary hemodynamics. Furthermore, in the rat fetus and neonate, endothelial cells expressed the gene for tropoelastin and hence probably play a significant role in the formation of internal elastic lamina in vivo.
Am J Respir Cell Mol Biol 1991 Dec
PMID:Developmental changes in tropoelastin gene expression in the rat lung studied by in situ hybridization. 172 Mar 20

Chronic pulmonary hypertension is associated with arterial structural remodeling. Insulin-like growth factor I (IGF-I) has been proposed as one of the mediators of vascular change because of its ability to stimulate proliferation in, and elastin production by, cultured vascular smooth muscle cells. We have shown previously that 12 days of continuous air embolization into the pulmonary arterial circulation of sheep results in the functional and structural changes of chronic pulmonary hypertension. In the present study, measurements of IGF-I (by radioimmunoassay) and IGF-I binding protein activity in sheep lung lymph and plasma were made before and during the 12 days of air embolization in six sheep. Two untreated animals served as controls. Baseline lung lymph contained 23.5 +/- 3.6 ng/ml (mean +/- SEM) of IGF-I, and there was a slight increase to 36.7 +/- 9.8 on day 3, but by day 6 levels were back to baseline. The flux of IGF-I from the lung (concentration times lymph flow) increased significantly by day 2 embolization and remained elevated through day 12 (baseline = 37.2 +/- 11.1 ng/15 min; day 2 = 237.7 +/- 55.8; day 5 = 190.2 +/- 53.4; day 6 = 82.6 +/- 21.9; day 12 = 78.7 +/- 12.5). IGF-I binding protein activity was also present in lung lymph at baseline (29.6 +/- 3.0%) and was unchanged during air embolization. Plasma levels of IGF-I and plasma binding protein activity remained at baseline throughout the 12 days of embolization (71.51 +/- 34.48 ng/ml and 36.4 +/- 3.5%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jan
PMID:Insulin-like growth factor I and pulmonary hypertension induced by continuous air embolization in sheep. 172 99

The full elastolytic phenotype of Pseudomonas aeruginosa requires lasB, the structural gene for elastase, its transcriptional activator lasR, and lasA. The lasB gene was insertionally inactivated with the omega fragment and this mutated gene introduced into the P. aeruginosa chromosome. Replacement of the wild-type gene with the inactivated gene was verified by Southern analysis and confirmed by lack of elastase antigen on Western blots and lack of activity in liquid assays. The mutant did, however, retain elastolytic activity on elastin plates. This residual activity was abolished by inactivation of lasB in PAO-E64, a lasA-deficient mutant, demonstrating that it was due to the lasA gene product. Northern analysis demonstrated that, like lasB, lasA is transcriptionally controlled by the lasR gene product.
Mol Microbiol 1991 Aug
PMID:Pseudomonas aeruginosa LasA: a second elastase under the transcriptional control of lasR. 176 76

The extracellularly secreted endopeptidase elastase (LasB) is regarded as an important virulence factor of Pseudomonas aeruginosa. It has also been implicated in the processing of LasA which enhances elastolytic activity of LasB. In order to investigate the role of LasB in virulence and LasA processing, a LasB-negative mutant, PAO1E, was constructed by insertional mutagenesis of the LasB structural gene, lasB, in P. aeruginosa PAO. An internal 636 bp lasB fragment of the plasmid pRB1803 was ligated into a derivative of the mobilization vector pSUP201-1. The resulting plasmid, pBRMOB-LasB, was transformed into Escherichia coli and transferred by filter matings to the LasB-positive P. aeruginosa strain, PAO1. Plasmid integration in the lasB site of the chromosome was confirmed by Southern blot analysis. Radioimmunoassay and immunoblotting of PAO1E supernatant fluids yielded no detectable LasB (less than 1 ng ml-1 LasB). The absence of LasB in PAO1E was further proven by the inability of its culture supernatant fluid to cleave transferrin or rabbit immunoglobulin G (IgG) after a 72 h incubation. The residual proteolytic activity of PAO1E culture supernatant fluid was attributed to alkaline proteinase (Apr), since it was totally inhibited by specific antibodies against Apr. Residual elastolytic activity in culture supernatant fluid of PAO1E was due to the LasA fragment and to the combined action of the LasA fragment with Apr on elastin. The sizes of purified LasA from PAO1 and PAO1E were identical (22 kDa). These results show that, besides LasB and the LasA fragment, Apr may also act on elastin in the presence of the LasA fragment and that the proteolytic processing of LasA in P. aeruginosa is independent of LasB.
Mol Microbiol 1991 Sep
PMID:Pseudomonas aeruginosa LasB mutant constructed by insertional mutagenesis reveals elastolytic activity due to alkaline proteinase and the LasA fragment. 176 84


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