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)

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

The connective tissue network in striated muscle, consisting principally of collagen is arranged in a three dimensional network and is intimately associated with muscle function. Previous studies have shown that animals maintained on a copper-deficient diet undergo myocardial hypertrophy and exhibit cardiovascular lesions such as ventricular aneurysms that eventually rupture. A deficiency of copper in the diet is known to inhibit lysyl oxidase, a metalloenzyme requiring copper as a cofactor and which is also responsible for collagen and elastin crosslinking. Examination by scanning and transmission electron microscopy of skeletal and cardiac muscle from rats maintained on copper-deficient diets showed both gross and microscopic lesions to the connective tissue network. Immunohistochemical staining by light microscopy with antibodies against lysyl oxidase showed that the enzyme was equally present in both control and experimental animals. Fluorescent staining for antibodies against collagen types I and III showed similar results. From these studies we concluded that the collagen secreted during hypertrophy was not crosslinked by lysyl oxidase due to the absence of the copper cofactor. This resulted in the failure of the connective tissue network to transmit and distribute the increased force associated with myocardial hypertrophy and resulted in myocardial aneurysms.
J Mol Cell Cardiol 1985 Dec
PMID:Alteration of the connective tissue network of striated muscle in copper deficient rats. 286 28

We have studied the effects of beta-aminopropionitrile (BAPN) administration on the formation of spontaneous arterial lesions, characterized principally by a rupture in the internal elastic lamina (IEL) in the caudal and renal arteries of the Wistar rat. Treatment with BAPN (an inhibitor of lysyl oxidase) increased the formation of these lesions in rats up to 12 weeks of age but had differential effects on the caudal and renal artery in older rats. Administration of the nitrile to weanling rats led to the premature formation of lesions in caudal arteries of both male and female rats which morphologically resemble lesions which form spontaneously later in life. Dietary supplements of copper or pyridoxine were without effect on the formation of spontaneous caudal artery lesions when given from 5 wks of age but a copper supplement from midgestation slightly inhibited lesion formation only in male rats. This suggests that if copper deficiency is involved in spontaneous lesion formation, it is only a contributory factor. Quantification of either caudal or renal artery lesions within different litters of Wistar rats showed that there exists a familial aggregation in the frequency of spontaneous lesion formation, certain litters showing significantly higher levels of lesions than others. Adult Sprague-Dawley rats also appear to be more susceptible to the development of renal artery IEL defects than Wistar rats. The possibility of a hereditary disorder leading to a minor defect in elastic fibre structure which could be responsible for the spontaneous lesions is discussed.
Exp Mol Pathol 1986 Oct
PMID:Spontaneous arterial lesions involving breaks in the internal elastic lamina in the rat: effects of beta-aminopropionitrile and familial distribution. 377 Jan 43

Assays of serum benzylamine oxidase (BzAO) have led some workers to postulate a relationship between elevated BzAO activity and diseases characterized by proliferating connective tissue. The present study was designed to determine whether BzAO activity of a cellular tissue is also affected. BzAO was assayed in homogenates of normal and atherosclerotic human aortae. Characterization done in normal aortae showed that BzAO is not a classical monoamine, diamine, polyamine, or lysyl oxidase, nor is it a ceruloplasmin. The enzyme is heat stable at 60 degrees C and is associated primarily with the microsomal fraction on density centrifugation. Compared with phenylethylamines and indoleamines, benzylamine is the best substrate. BzAO is sensitive to inhibition by hydrazines and chymotrypsin but not trypsin, and is insensitive to Triton X-100 and sulfhydryl-group blockade. BzAO activity of atherosclerotic plaque (expressed per gram wet weight or per milligram protein) was decreased markedly compared to that in adjacent, nonplaque regions and in normal aortae. However, on a per milligram DNA basis, the BzAO activity of plaque did not differ from that of nonplaque tissue. We conclude that there is a decreased cell population density in plaque, a contention supported by kinetic analysis. Plaque BzAO showed a decreased Vmax with no change in the Km of benzylamine compared with nonplaque tissue. Thus, if a relationship exists between BzAO activity and proliferating connective tissue, it is not apparent at the level of the cellular enzyme in atherosclerotic aortae of man.
Exp Mol Pathol 1983 Apr
PMID:Benzylamine oxidase in normal and atherosclerotic human aortae. 683 47

Lysyl oxidase, a copper-dependent metalloenzyme, plays a central role in crosslinking of collagen and elastin in the extracellular matrix. Notably, lung lysyl oxidase activity is markedly stimulated in rats exposed to cadmium vapors. To further understand the mechanism of cadmium toxicity, the mRNA expression, synthesis, post-translational processing, and catalytic activity of lysyl oxidase were examined in cadmium-resistant (CdR) cells and the cadmium-sensitive Swiss mouse 3T3 cells from which they were derived. These CdR cells synthesized and accumulated markedly elevated levels of metallothionein, a known marker for cadmium resistance, whereas the expression of lysyl oxidase was reduced considerably. In comparison to the parental, cadmium-sensitive cells, the suppression of enzyme production in the CdR cells was seen at the mRNA level, at the levels of intracellular proprotein production and mature enzyme secreted into the medium, and in terms of total enzyme activity in the culture. The presence of cupric chloride in the culture medium during the incubation of the CdR cells for 16 h significantly enhanced lysyl oxidase activity accumulating in the medium, suggesting that lysyl oxidase deficiency in CdR cells may be related to abnormal copper metabolism.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Downregulation of lysyl oxidase in cadmium-resistant fibroblasts. 754 71

Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle alpha-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase-3), and collagenase I (matrix metalloproteinase-1) mRNA but undetectable levels of lysyl oxidase mRNA. Partial restoration of lysyl oxidase transcription was observed in four of five phenotypic revertants derived from rat FE-8 and NIHpEJcl3 cells. The elevated levels of transin mRNA found in NIHpEJcl3 cells were diminished to the pretransformation level in interferon revertants but were not reduced in phenotypic rat FE-8 revertants expressing a high level of the ras oncoprotein. High steady-state levels of collagenase I mRNA were dependent on ras expression but were not closely associated with the transformed phenotype. High levels of cathepsin L mRNA were associated with neither high ras expression nor neoplastic transformation. The downregulation of smooth-muscle alpha-actin, characteristic of transformed cell lines, was not reversible in phenotypic revertants.
Mol Carcinog 1995 Apr
PMID:Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants. 772 41

Lysyl oxidase initiates crosslink formation of the collagen and elastin extracellular matrix, thereby delimiting its expansive properties. Recently lysyl oxidase has been cloned from several species enabling the computation of the relative order of appearance of the various components of this enzyme system. Comparative evolutionary computer-assisted sequence analysis of the enzyme and its various substrates was undertaken to address this issue. These results support the ordered genesis of the collagen substrate-->lysyl oxidase enzyme-->elastin substrate.
Comp Biochem Physiol Biochem Mol Biol 1994 May
PMID:The origin of lysyl oxidase. 791 84

The regulation of lysyl oxidase produced by cultured, lipid-enriched, neonatal rat lung fibroblasts was explored. The presence of 40 pM of transforming growth factor-beta 1 (TGF-beta 1) in overnight cultures increased levels of enzyme secreted into the medium by 1.6-fold while steady-state levels of lysyl oxidase mRNA increased similarly. In contrast, incubation of these cultures with 100 nM of prostaglandin E2 (PGE2) reduced enzyme activity levels by 40 to 50% although steady-state mRNA was not changed. Consistent with the effect of PGE2, the presence of indomethacin stimulated levels of secreted enzyme activity. When present in cultures simultaneously with TGF-beta 1, PGE2 prevented the stimulation beyond control levels seen with TGF-beta 1 alone. Densitometry of protein bands immunoprecipitated by antibody to lysyl oxidase indicated that the degree of conversion of the 50 kD proenzyme to the 29 kD enzyme was not significantly altered by TGF-beta 1 or PGE2. However, the net accumulation of all forms of lysyl oxidase protein was increased by TGF-beta 1 and decreased by PGE2. These results indicate that TGF-beta 1 and specific prostaglandin(s) exert opposing effects on the expression of lysyl oxidase in these lung fibroblasts.
Am J Respir Cell Mol Biol 1994 Dec
PMID:Regulation of lysyl oxidase expression in lung fibroblasts by transforming growth factor-beta 1 and prostaglandin E2. 794 3

We have isolated the entire gene coding for human lysyl oxidase. Coding and untranslated domains of human lysyl oxidase mRNA were found in 7 exons, distributed throughout approximately 14 kb of human genomic DNA. The appearance of exon sequences in lysyl oxidase mRNA in several human tissues was determined using a reverse transcriptase - PCR assay. In contrast to a previous report, this analysis has unambiguously shown that the size heterogeneity of lysyl oxidase mRNA was not due to alternate usage of any of the exons of the lysyl oxidase gene. Moreover, DNA sequence analysis of the entire 3.8 kb 3'-untranslated region (UTR) within exon 7 revealed multiple poly-adenylation sites which were shown to be differentially expressed in human skin fibroblasts. This differential usage of polyadenylation sites within the 3'-UTR explains the appearance of multiple lysyl oxidase mRNAs of different sizes.
Mol Biol Rep 1995
PMID:The size heterogeneity of human lysyl oxidase mRNA is due to alternate polyadenylation site and not alternate exon usage. 853 27

Lysyl oxidase (EC 1.4.3.13) plays a pivotal role in the maintenance of tissue integrity in both the normal and pathological states. It is a member of a newly discovered gene family that exhibits a complex mode of regulation. To date the resources necessary to begin to address its regulation have not been assembled. In part, this reflects the instability of this region of the genome when cloned into cosmid vectors. The paucity of long range restriction endonuclease sites suitable for mapping this region of the genome has further hampered progress. To begin to address this issue 2 YAC clones of 920 kb and 245 kb that contain the human lysyl oxidase gene were isolated. Long range physical mapping revealed that the 245 kb clone was centrally located within the 920 kb clone. The corresponding map of this region is congruent with that observed in the human genome. Thus, these YACs faithfully represent this region of the human genome. The results of our cloning and mapping studies described in this communication should accelerate the advance of our understanding of this new connective tissue gene family.
J Mol Cell Cardiol 1995 Oct
PMID:Isolation and characterization of a 1 Mb region of 5q23.3-q31.2 surrounding the human lysyl oxidase gene. 857 56


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