Disease relevance of LOXL1

• In conclusion, the LOL protein was identified as a secreted protein and localized in the extracellular matrix in active fibrotic diseases and in the early stromal reaction of breast cancer [1].
• Purification of enzymatically active human lysyl oxidase and lysyl oxidase-like protein from Escherichia coli inclusion bodies [2].
• Induction of fibrosis in vivo by lysyl oxidase-like enzymes has never been observed before and suggests that LOR-1 may function as an autonomous inducer of fibrosis [3].
• Coexpression of the lysyl oxidase-like gene (LOXL) and the gene encoding type III procollagen in induced liver fibrosis [4].
• Fibroblasts, smooth muscle and osteosarcoma (HOS) cells express LOXL4 [5].

High impact information on LOXL1

• Elastic fiber homeostasis requires lysyl oxidase-like 1 protein [6].
• Deposition of fibulin-5 on microfibrils promotes coacervation and alignment of tropoelastins on microfibrils, and also facilitates cross-linking of tropoelastin by tethering lysyl oxidase-like 1, 2, and 4 enzymes [7].
• Using BLASTN searches, we identified a LOXL3 variant LOXL3-sv1 that lacked the sequences corresponding to exons 1, 2, 3, and 5 of LOXL3 [8].
• These findings strongly indicate that LOXL3 encodes two variants, LOXL3 and LOXL3-sv1, both of which function as amine oxidases with distinct tissue and substrate specificities from one another [8].
• A Tissue-specific Variant of the Human Lysyl Oxidase-like Protein 3 (LOXL3) Functions as an Amine Oxidase with Substrate Specificity [8].

Chemical compound and disease context of LOXL1

• We have isolated a mouse lysyl oxidase-like (LOXL) cDNA from a mouse embryo cDNA library and used this cDNA to measure changes in steady state levels of LOXL mRNA during the development of carbon tetrachloride-induced liver fibrosis in adult mice [4].

Biological context of LOXL1

• These data provide physical mapping information to complement the previous cytogenetic localization of LOXL1 [9].
• Thus by term, LOX was expressed predominantly in the amniotic epithelium, with little expression in the placenta, while LOXL showed highest gene expression in the placenta and lowest expression in the amnion [10].
• This lysyl oxidase-like gene, which appears to be no larger than 22.1 kilobases, codes for a single polyadenylated RNA species of 2.48 kilobases and has been mapped to chromosome 15q24-q25 [11].
• Restriction mapping and DNA sequence analysis revealed that the complete sequence of the lysyl oxidase-like mRNA was encoded by seven exons distributed throughout 25 kilobases of genomic DNA [12].
• Indeed, recent findings reveal that LOX and LOXL proteins markedly influence cell behavior including chemotactic responses, proliferation, and shifts between the normal and malignant phenotypes [13].

Anatomical context of LOXL1

• Full-length LOX/LOXL and constructs containing just the pro-regions of each enzyme localized to elastic fibers when expressed in cultured cells [14].
• Lysyl oxidase-like and lysyl oxidase are present in the dermis and epidermis of a skin equivalent and in human skin and are associated to elastic fibers [15].
• We screened a library of about 1000 active ingredients to find activators capable to stimulate specifically the LOXL gene expression in adult dermal fibroblasts [16].
• RESULTS: LOX and LOXL were identified, by Western blotting and immunofluorescence, and LO activity was measured in the medium, with both proliferative and hypertrophic chondrocytes [17].
• The purpose of this study was to verify the difference between carrying a load on the sacrum (LOS) and on the lumbar vertebrae (LOL) in oxygen uptake, muscle activities, heart rate, cadence, and subjective response [18].

Associations of LOXL1 with chemical compounds

• A novel human lysyl oxidase-like gene (LOXL4) on chromosome 10q24 has an altered scavenger receptor cysteine rich domain [5].
• The LOXL3 protein contains four scavenger receptor cysteine-rich domains in the N terminus in addition to the C-terminal characteristic domains of the LOX family, such as a copper binding domain, a cytokine receptor-like domain and residues for the lysyl-tyrosyl quinone cofactor [8].
• The lysyl oxidase-like protein 4 (LOXL4) is the latest member of the emerging family of lysyl oxidases, several of which were shown to function as copper-dependent amine oxidases catalyzing lysine-derived cross-links in extracellular matrix proteins [19].
• The purified LOXL4 proteins showed beta-aminopropionitrile-inhibitable activity of 0.022-0.032 units/mg toward a nonpeptidyl substrate, benzylamine [19].
• Moreover, gallic acid, chlorogenic acid, and caffeic acid, which are plant polyphenols, converted the lysine residue of bovine serum albumin to alpha-amino-adipic semialdehyde residue, indicating lysyl oxidase-like activity [20].

Other interactions of LOXL1

• The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues [21].
• We report here the complete cDNA sequence and exon-intron organization of the human lysyl oxidase-like (LOXL)3 gene, a new member of the lysyl oxidase (LO) gene family [22].
• Pulsed-field gel electrophoresis showed comigrating bands for both the PML cDNA and LOXL1 probes, demonstrating a physical linkage between these two genes [9].
• The human lysyl oxidase-like gene maps between STS markers D15S215 and GHLC.GCT7C09 on chromosome 15 [23].
• After amplification and sequencing of the 5'end of the fis clone, subsequent database searches showed an exact match with the coding sequence of the human lysyl oxidase-like gene 4 (LOXL4) [24].

Analytical, diagnostic and therapeutic context of LOXL1

• An exon probe identified a single transcript of 2.4 kb on a multitissue Northern blot with a pattern identical to the one reported for the LOXL1 gene [9].
• Ligand blot and mammalian two-hybrid assays confirmed an interaction between tropoelastin and the pro-regions of both LOX and LOXL [14].
• Using the PCR primers generated from human expressed sequence tag (EST), the cDNA of lysyl oxidase-like gene 3 (LOXL3), a new member of human lysyl oxidases gene family, was cloned from the human fetal brain mRNA [25].
• The LOX and LOXL mRNA level, quantified by real-time reverse transcriptase-polymerase chain reaction decreased in adult skin fibroblasts compared with fibroblasts from children [16].
• Before surgery, patients were randomly assigned to three groups: (1) conventional mechanical ventilation (CV), (2) OLC started after arrival on the ICU (late open lung, LOL), and (3) OLC started directly after intubation (early open lung, EOL) [26].

References