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lysyl oxidase

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https://www.readbyqxmd.com/read/28538980/downregulation-of-lysyl-oxidase-protects-retinal-endothelial-cells-from-high-glucose-induced-apoptosis
#1
Dongjoon Kim, Robert P Mecham, Philip C Trackman, Sayon Roy
Purpose: To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods: Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to β-aminopropionitrile (BAPN), a LOX inhibitor...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28534485/pseudoexfoliation-syndrome-associated-genetic-variants-affect-transcription-factor-binding-and-alternative-splicing-of-loxl1
#2
Francesca Pasutto, Matthias Zenkel, Ursula Hoja, Daniel Berner, Steffen Uebe, Fulvia Ferrazzi, Johannes Schödel, Panah Liravi, Mineo Ozaki, Daniela Paoli, Paolo Frezzotti, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Shinichi Manabe, Erika Salvi, Paolo Manunta, Daniele Cusi, Christian Gieger, Heinz-Erich Wichmann, Tin Aung, Chiea Chuen Khor, Friedrich E Kruse, André Reis, Ursula Schlötzer-Schrehardt
Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28522596/lysyl-oxidase-overexpression-accelerates-cardiac-remodeling-and-aggravates-angiotensin-ii-induced-hypertrophy
#3
María Galán, Saray Varona, Anna Guadall, Mar Orriols, Miquel Navas, Silvia Aguiló, Alicia de Diego, María A Navarro, David García-Dorado, Antonio Rodríguez-Sinovas, José Martínez-González, Cristina Rodriguez
Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic mouse model with a strong cardiac expression of human LOX (TgLOX). TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast reprogramming...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522400/impact-of-lysyl-oxidase-g473a-polymorphism-on-diabetic-foot-ulcers
#4
Sivakamasundari Pichu, Jayalalitha Sathiyamoorthy, Selvaraj Vimalraj, Vijay Viswanathan, Suvro Chatterjee
Lysyl oxidase (LOX) is an extra-cellular matrix-modifying enzyme that has been linked to cell proliferation, metastasis, angiogenesis and wound healing. This study was designed to examine the association of LOX gene polymorphism G473A, G>A, (rs1800449) located in exon 1 of the LOX gene in diabetic subjects with and without diabetic foot ulcers (DFU) and its impact of expression on DFU. Genotypic analysis of 906 samples showed a significant increase in the presence of 'A' allele in type 2 diabetes mellitus (T2DM) and DFU when compared to that of control subjects...
May 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28508064/fibulin-4-is-essential-for-maintaining-arterial-wall-integrity-in-conduit-but-not-muscular-arteries
#5
Carmen M Halabi, Thomas J Broekelmann, Michelle Lin, Vivian S Lee, Mon-Li Chu, Robert P Mecham
Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4(E57K/E57K) mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28503365/genetics-diagnosis-and-monitoring-of-pseudoexfoliation-glaucoma
#6
Niraj Nathan, Rachel W Kuchtey
Recent studies have shed new light on the genetic factors underlying pseudoexfoliation syndrome, growing our understanding of the role of the lysyl oxidase-like 1 (LOXL1) gene and its various polymorphisms as well as identifying new genetic associations. Recent years have brought new insight on how these genetic factors interact with other factors, including environmental, to confer risk to individuals and populations worldwide. All of these findings may hold importance to the screening, diagnosis, and monitoring of pseudoexfoliation and may also help lead to the identification of novel therapeutic targets...
December 2016: Current Ophthalmology Reports
https://www.readbyqxmd.com/read/28495238/uncovering-the-role-of-nuclear-lysyl-oxidase-lox-in-advanced-high-grade-serous-ovarian-cancer
#7
Marta De Donato, Marco Petrillo, Enrica Martinelli, Flavia Filippetti, Gian Franco Zannoni, Giovanni Scambia, Daniela Gallo
OBJECTIVE: Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer...
May 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28485217/gaba-promotes-elastin-synthesis-and-elastin-fiber-formation-in-normal-human-dermal-fibroblasts-hdfs
#8
Eriko Uehara, Hideki Hokazono, Mariko Hida, Takako Sasaki, Hidekatsu Yoshioka, Noritaka Matsuo
The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner...
June 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28476896/altered-cargo-proteins-of-human-plasma-endothelial-cell-derived-exosomes-in-atherosclerotic-cerebrovascular-disease
#9
Edward J Goetzl, Janice B Schwartz, Maja Mustapic, Iryna V Lobach, Richard Daneman, Erin L Abner, Gregory A Jicha
Plasma endothelial cell-derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycoprotein VI. EDE levels of VCAM-1, von Willebrand factor, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, and lysyl oxidase-2 and the cerebrovascular-selective proteins glucose transporter 1, permeability-glycoprotein, and large neutral amino acid transporter 1 were significantly higher for 18 patients with cerebrovascular disease (CeVD) than for 18 age- and gender-matched control subjects...
May 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28471663/identification-of-4-aminomethyl-6-trifluoromethyl-2-phenoxy-pyridine-derivatives-as-potent-selective-and-orally-efficacious-inhibitors-of-the-copper-dependent-amine-oxidase-lysyl-oxidase-like-2-loxl2
#10
Martin W Rowbottom, Gretchen Bain, Imelda Calderon, Taylor Lasof, David Lonergan, Andiliy Lai, Fei Huang, Janice Darlington, Patricia Prodanovich, Angelina M Santini, Christopher D King, Lance Goulet, Kristen E Shannon, Gina L Ma, Katherine Nguyen, Deidre A MacKenna, Jilly F Evans, John H Hutchinson
LOXL2 catalyzes the oxidative deamination of ε-amines of lysine and hydroxylysine residues within collagen and elastin, generating reactive aldehydes (allysine). Condensation with other allysines or lysines drives the formation of inter- and intramolecular cross-linkages, a process critical for the remodeling of the ECM. Dysregulation of this process can lead to fibrosis, and LOXL2 is known to be upregulated in fibrotic tissue. Small-molecules that directly inhibit LOXL2 catalytic activity represent a useful option for the treatment of fibrosis...
May 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28471599/lysyl-oxidase-in-systemic-sclerosis-getting-under-the-skin
#11
Doron Rimar, Itzhak Rosner, Gleb Slobodin, Michael Rozenbaum, Lisa Kaly, Nina Boulman, Zahava Vadasz
No abstract text is available yet for this article.
September 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28468951/insulin-resistance-promotes-lysyl-oxidase-like-2induction-and-fibrosis-accumulation-in-nonalcoholic-fatty-liver-disease
#12
Paola Dongiovanni, Marica Meroni, Guido Alessandro Baselli, Giulia Alessandra Bassani, Raffaela Rametta, Alessandro Pietrelli, Marco Maggioni, Federica Facciotti, Valentina Trunzo, Sara Badiali, Silvia Fargion, Stefano Gatti, Luca Vittorio Carlo Valenti
Background & Aims: In patients with nonalcoholic fatty liver disease (NAFLD), insulin resistance (IR) associates with fibrosis progression independently of hepatic inflammation, but the mechanisms are still unclear. Methods : We modeled the independent contribution of inflammation (steatohepatitis: NASH) by exploiting the methionine-choline deficient (MCD) diet, and that of IR by insulin receptor haploinsufficiency (InsR+/-), in the pathogenesis of liver fibrosis in C57Bl/6 mice. We confirmed study findings in 96 patients with NAFLD...
May 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28467787/the-histone-deacetylase-inhibitor-romidepsin-as-a-potential-treatment-for-pulmonary-fibrosis
#13
Franco Conforti, Elizabeth R Davies, Claire J Calderwood, Thomas H Thatcher, Mark G Jones, David E Smart, Sumeet Mahajan, Aiman Alzetani, Tom Havelock, Toby M Maher, Philip L Molyneaux, Andrew J Thorley, Teresa D Tetley, Jane A Warner, Graham Packham, A Ganesan, Paul J Skipp, Benjamin J Marshall, Luca Richeldi, Patricia J Sime, Katherine M A O'Reilly, Donna E Davies
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials...
April 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453968/association-of-altered-collagen-content-and-lysyl-oxidase-expression-in-degenerative-mitral-valve-disease
#14
K-Raman Purushothaman, Meerarani Purushothaman, Irene C Turnbull, David H Adams, Anelechi Anyanwu, Prakash Krishnan, Annapoorna Kini, Samin K Sharma, William N O'Connor, Pedro R Moreno
BACKGROUND: Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity. METHODS: Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls...
April 12, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28452589/lysyl-oxidase-propeptide-promotes-adipogenesis-through-inhibition-of-fgf-2-signaling
#15
John D Griner, Carl J Rogers, Mei-Jun Zhu, Min Du
Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine residues in collagen and elastin, key components of connective tissue. LOX is synthesized as an inactive 50 kD pre-proenzyme, and secreted to the extracellular matrix where it is cleaved into an active 32 kD LOX, and an 18kD free propeptide (LOX-PP), purportedly an inhibitor of fibroblast growth factor-2 (FGF-2) signaling. Given that adipocytes are distributed inside the connective tissue, it is likely that LOX-PP has an important regulatory role in adipogenesis, which has not been studied...
January 2, 2017: Adipocyte
https://www.readbyqxmd.com/read/28449718/hif-1%C3%AE-promoted-vasculogenic-mimicry-formation-in-hepatocellular-carcinoma-through-loxl2-up-regulation-in-hypoxic-tumor-microenvironment
#16
Meili Wang, Xiulan Zhao, Dongwang Zhu, Tieju Liu, Xiaohui Liang, Fang Liu, Yanhui Zhang, Xueyi Dong, Baocun Sun
BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) have steadily increased in recent years. A hypoxic microenvironment is one of the most important characteristics of solid tumors which has been shown to promote tumor metastasis, epithelial-mesenchymal transition and angiogenesis. Epithelial-mesenchymal transition and vasculogenic mimicry have been regarded as crucial contributing factors to cancer progression. HIF-1α functions as a master transcriptional regulator in the adaptive response to hypoxia...
April 27, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28445745/increased-tissue-stiffness-in-tumors-from-mice-with-neurofibromatosis-1-optic-glioma
#17
Christopher Walter, Lindsey Crawford, Melinda Lai, Joseph A Toonen, Yuan Pan, Shelly Sakiyama-Elbert, David H Gutmann, Amit Pathak
Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#18
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28439422/anti-aging-effect-and-gene-expression-profiling-of-dung-beetle-glycosaminoglycan-in-aged-rats
#19
Mi Young Ahn, Ban Ji Kim, Ha Jeong Kim, Jae Sam Hwang, Yi-Sook Jung, Kun-Koo Park
BACKGROUND: This study aimed to evaluate the anti-aging effect of a newly prepared insect-derived compound, dung beetle glycosaminoglycan (GAG), given intraperitoneally to old SD rats as part of their diet for 1 month. Insect GAG administration was found to be related to a reduction in oxidative damage, hepato-cellular biomarker levels, protein carbonyl content, and malondialdehyde concentration. The anti-aging-related molecular genetic mechanisms of dung beetle GAG are not yet fully elucidated...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/28435530/small-molecule-lysyl-oxidase-like-2-loxl2-inhibitors-the-identification-of-an-inhibitor-selective-for-loxl2-over-lox
#20
John H Hutchinson, Martin W Rowbottom, David Lonergan, Janice Darlington, Pat Prodanovich, Christopher D King, Jilly F Evans, Gretchen Bain
Two series of novel LOXL2 enzyme inhibitors are described: benzylamines substituted with electron withdrawing groups at the para-position and 2-substituted pyridine-4-ylmethanamines. The most potent compound, (2-chloropyridin-4-yl)methanamine 20 (hLOXL2 IC50 = 126 nM), was shown to be selective for LOXL2 over LOX and three other amine oxidases (MAO-A, MAO-B, and SSAO). Compound 20 is the first published small molecule inhibitor selective for LOXL2 over LOX.
April 13, 2017: ACS Medicinal Chemistry Letters
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