Disease relevance of LOX

• Irreversible inhibition of lysyl oxidase by homocysteine thiolactone and its selenium and oxygen analogues. Implications for homocystinuria [1].

High impact information on LOX

• A previously unknown redox cofactor has been identified in the active site of lysyl oxidase from the bovine aorta [2].
• Lysyl oxidase was similarly localized in newborn rat aorta at the interface between microfibrils and nascent elastin fibers [3].
• Ultrastructural immunolocalization of lysyl oxidase in vascular connective tissue [3].
• Characterization of the native lysine tyrosylquinone cofactor in lysyl oxidase by Raman spectroscopy [4].
• The activities of plasma amine oxidase and diamine oxidase were only minimally reduced at concentrations of the sulfur or selenium lactones that fully inhibited lysyl oxidase [1].

Biological context of LOX

• Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted amino acid sequence [5].
• Hydrogen peroxide-mediated, lysyl oxidase-dependent chemotaxis of vascular smooth muscle cells [6].
• Modulation of lysyl oxidase substrate specificity by the oleate anion [7].
• The first step in normal cross-linking in elastin is the formation of alpha-aminoadipic-delta-semialdehyde, allysine, through oxidative deamination of specific peptidyl lysine by the enzyme lysyl oxidase (EC 1.4.3.13) [8].
• Kinetics and stereospecificity of the lysyl oxidase reaction [9].

Anatomical context of LOX

• Accelerated calcification represses the expression of elastic fiber components and lysyl oxidase in cultured bovine aortic smooth muscle cells [10].
• The addition of LO to VSMC elevated the levels of intracellular H(2)O(2), enhanced stress fiber formation, and focal adhesion assembly, is consistent with the induction of the chemotactic response [6].
• In vitro transcription of the cloned lysyl oxidase cDNA and cell-free translation of its mRNA transcript yielded a 47-kDa protein in the absence and a 50-kDa glycosylated protein in the presence of pancreatic membranes, each of which were immunoprecipitated with antibody against the 32-kDa bovine enzyme [11].
• A possible pathway by which LO can enter cell nuclei was explored in the present study [12].
• 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 [13].

Associations of LOX with chemical compounds

• LO-dependent chemotaxis, but not chemokinesis, was abolished by beta-aminopropionitrile, an active site inhibitor of LO, or by catalase, as well as by prior heat denaturation [6].
• This indicates that the H(2)O(2) product of amine oxidation by LO is critical to the expression of its chemotactic activity [6].
• This finding suggests that lysine residues in an individual cross-linking domain may not have equal susceptibility to oxidation by lysyl oxidase [14].
• Lysyl oxidase initiates the covalent cross-linking of elastin and collagen, converting lysyl residues in these proteins to peptidyl aldehyde residues [15].
• Reaction of lysyl oxidase with trans-2-phenylcyclopropylamine [16].

Other interactions of LOX

• TE, FBN1, and LO mRNA levels, assessed by reverse transcription-polymerase chain reaction, were also decreased by exposure to 10 mM beta-GP [10].
• Such stereospecificity and proton exchange uniquely differentiates lysyl oxidase from all but an aortic semicarbazide-sensitive amine oxidase among the pro-S-specific copper-dependent amine oxidases analyzed thus far [9].
• These results suggest that heparin may modulate the oxidation and thus the insolubilization of extracellular collagen fibers, possibly under conditions where elastin fiber synthesis is not affected, and that the tight binding of lysyl oxidase to collagen is not completely related to the expression of enzyme activity toward this substrate [17].
• Special reference is made to cytochrome c oxidase, lysyl oxidase, superoxide dismutase and endoplasmic reticulum enzymes and to their role in the expression of disease [18].

Analytical, diagnostic and therapeutic context of LOX

• Northern blots screened with lysyl oxidase cDNA probes identified hybridizing species of 5.8 and 4.5 kb in mRNA of rat aorta and lung, while dot blot analyses were negative for lysyl oxidase mRNA in preparations of rat brain, liver, kidney, and heart [5].
• Although this domain contains the characteristic paired lysine residues found in other cross-linking domains of elastin, protein sequence analysis indicated that the first but not the second lysine had been oxidized by lysyl oxidase [14].
• Evidence for pyrroloquinolinequinone as the carbonyl cofactor in lysyl oxidase by absorption and resonance Raman spectroscopy [19].
• Such similarity also exists between the peptide maps of the aortic enzyme and the urea-extractable lysyl oxidase of bovine cartilage, as well as with the peptide maps of a catalytically quiescent protein resolved from the aortic enzyme by gel exclusion chromatography [20].
• Lysyl oxidase mRNA expression was investigated with semi-quantitative RT-PCR, whilst expression of cytochrome P450 17alpha-hydroxylase and cytochrome P450 side-chain cleavage mRNA was examined using real time PCR [21].

References