Disease relevance of Lox

• These results suggest that upregulation by CSC of cellular thiols may play an important role in the downregulation of LO and subsequently destabilization of the lung ECM in CS-induced emphysema [1].
• Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat [2].
• Accumulation of extracellular matrix is a major factor in growth of the restenotic lesion, and modulation of lysyl oxidase activity may offer a therapeutic method for decreasing or preventing recurrent stenosis [3].
• 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 [4].
• These results are the first to provide evidence for a time-dependent appearance of active extracellular lysyl oxidase in brain injury sites [5].

High impact information on Lox

• Lysyl oxidase (EC 1.4.3.13) oxidizes peptidyl lysine to peptidyl aldehyde residues within collagen and elastin, thus initiating formation of the covalent cross-linkages that insolubilize these extracellular proteins [6].
• The present study provides evidence by immunocytochemical confocal microscopy, Western blot analysis, enzyme assays, and chemical analyses for lysyl oxidase reaction products that this enzyme is present and active within rat vascular smooth muscle cell nuclei [6].
• These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition [2].
• Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space [2].
• beta-Aminopropionitrile, a specific inhibitor of lysyl oxidase prevented the rise in blood pressure induced by deoxycorticosterone-salt in rats [7].

Chemical compound and disease context of Lox

• Collagen lysyl oxidase activity in the lung increases during bleomycin-induced lung fibrosis [8].
• To define the role of this process in kidney fibrosis, we investigated the renal expression of lysyl oxidase and the content in collagen cross-links at various stages of chronic Adriamycin nephropathy in Sprague-Dawley rats [9].
• However, SB 209670 did not significantly affect infarct size, compensatory cardiac hypertrophy, nor the myocardial mRNA levels of procollagen type I and III, and prolyl 4-hydroxylase and lysyl oxidase, 2 important enzymes affecting collagen secretion, stability and functionality [10].
• When beta-aminopropionitrile, a specific inhibitor of lysyl oxidase, was administered before the onset of DOCA-salt hypertension, the aortic collagen content was reduced markedly [11].
• The altered tissue amounts of lysyl oxidase and prolyl hydroxylase after cadmium inhalation correlated well with the marked interstitial cell hyperplasia 4 to 5 days after exposure and suggested that connective tissue protein synthesis is activated in the interstitial cell fibroblasts soon after cadmium exposure [12].

Biological context of Lox

• Altered adhesion features and signal transduction in NRK-49F cells transformed by down-regulation of lysyl oxidase [13].
• Lysyl oxidase gene expression and enzyme activity in the rat ovary: regulation by follicle-stimulating hormone, androgen, and transforming growth factor-beta superfamily members in vitro [14].
• Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted amino acid sequence [15].
• Downregulation of lysyl oxidase and upregulation of cellular thiols in rat fetal lung fibroblasts treated with cigarette smoke condensate [1].
• Interestingly, the nonconsensus polyadenylations in rat did not occur at the same positions as was found in mouse lysyl oxidase cDNAs [16].

Anatomical context of Lox

• LOX mRNA is abundantly expressed in rat granulosa cells [14].
• PKC-MEK-MAPK-dependent signal transduction pathway mediates the stimulation of lysyl oxidase expression by serum and PDGF in rat aortic smooth muscle cells [17].
• Lysyl oxidase staining increased until 72 hours after bile duct ligation, when it was located in areas surrounding the myofibroblastic cells [18].
• Mechanical strength doubled over weeks 4-5 when production of collagen and elastic fibers and expression of lysyl oxidase were subsiding [19].
• CONCLUSION: Our results indicate that lysyl oxidase mRNA and protein expression is time-dependent after balloon injury of the rat carotid artery and that expression appears to precede maximal collagen accumulation and corresponding increases in intimal area [3].

Associations of Lox with chemical compounds

• Dihydrotestosterone alone enhanced LOX mRNA and enzyme activity, but potentiated the effect of FSH, causing a further reduction [14].
• Interestingly, exposure of cells to glutathione monoethyl ester, a GSH delivery system, effectively elevated cellular GSH levels and induced a dose-dependent decrease in levels of the protein species and catalytic activity of LO [1].
• Regulation of lysyl oxidase expression in lung fibroblasts by transforming growth factor-beta 1 and prostaglandin E2 [20].
• The increase of lysyl oxidase activity preceded the maximal increase of total lung hydroxyproline and desmosine which occurred 28 days after bleomycin instillation [8].
• DHEA treatment increased LOX mRNA expression to more than three times the control value (P: < 0.01) [21].

Physical interactions of Lox

• Lysyl oxidase may also serve as a vehicle for copper transport from extracellular matrix cells [22].

Enzymatic interactions of Lox

• Lysyl oxidase catalyzes the crosslinking of collagen and elastin [2].
• Lysyl oxidase is an extracellular enzyme that catalyzes cross-linkages of extracellular matrix proteins [5].

Regulatory relationships of Lox

• PURPOSE: This investigation was designed to test the hypothesis that transforming growth factor-beta 1 (TGF-beta 1) regulates lysyl oxidase secretion from vascular smooth muscle cells [23].

Other interactions of Lox

• Lysyl oxidase (LOX) catalyzes the final enzymatic reaction required for cross-linking of collagen and elastin fibers and therefore has a crucial role in regulating the formation and maintenance of extracellular matrix in the ovary [14].
• Growth differentiation factor-9 (GDF-9) and activin A, at the same concentration as TGFbeta1 (10 ng/ml), stimulated LOX mRNA and activity within 6 h, although overall expression was higher at 48 h [14].
• There was a strong up-regulation of lysyl oxidase expression during weeks 1-3 with a peak in expression at week 3, correlating with the phases of collagen and tropoelastin production [19].
• The effect of TGF-beta 1 on lysyl oxidase in vascular smooth muscle cells has not been previously defined [23].
• Matrix metalloproteinase (MMP) and lysyl oxidase activity were assayed in the conditioned medium [24].

Analytical, diagnostic and therapeutic context of Lox

• 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 [20].
• Northern blot analyses were performed to determine steady-state levels of lysyl oxidase mRNA in the smooth muscle cells [23].
• Lysyl oxidase levels were estimated in rat tissues using an enzyme-linked immunosorption assay (ELISA) and a functional assay standardized against known amounts of purified lysyl oxidase [25].
• Steady-state lysyl oxidase mRNA levels were quantitated with real-time reverse transcription polymerase chain reaction (TaqMan) [3].
• Lysyl oxidase activity in the media was quantitated with a tritium-release bioassay against an insoluble 3H-labeled aortic clastin substrate [23].

References