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lysyl oxidase

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https://www.readbyqxmd.com/read/28225063/targeted-inhibition-of-focal-adhesion-kinase-attenuates-cardiac-fibrosis-and-preserves-heart-function-in-adverse-cardiac-remodeling
#1
Jie Zhang, Guangpu Fan, Hui Zhao, Zhiwei Wang, Fei Li, Peide Zhang, Jing Zhang, Xu Wang, Wei Wang
Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220932/a-phase-2-study-of-simtuzumab-in-patients-with-primary-post-polycythaemia-vera-or-post-essential-thrombocythaemia-myelofibrosis
#2
Srdan Verstovsek, Michael R Savona, Ruben A Mesa, Hua Dong, Julia D Maltzman, Shringi Sharma, Jeffrey Silverman, Stephen T Oh, Jason Gotlib
Simtuzumab, a monoclonal antibody inhibitor of extracellular matrix enzyme lysyl oxidase-like-2, showed preclinical promise and was well tolerated in clinical studies. A phase 2, open-label study of simtuzumab was conducted in patients with primary myelofibrosis (MF), post-polycythaemia vera MF and post-essential thrombocythaemia MF. Fifty-four patients were randomized to receive simtuzumab alone (200 or 700 mg [n = 12 each group]) or simtuzumab (200 or 700 mg) with ruxolitinib (n = 15 each group) for 24 weeks...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28203099/a-new-dermocosmetic-containing-retinaldehyde-delta-tocopherol-glucoside-and-glycylglycine-oleamide-for-managing-naturally-aged-skin-results-from-in-vitro-to-clinical-studies
#3
Céline Rouvrais, Daniel Bacqueville, Patrick Bogdanowicz, Marie-José Haure, Laure Duprat, Christine Coutanceau, Nathalie Castex-Rizzi, Hélène Duplan, Valérie Mengeaud, Sandrine Bessou-Touya
INTRODUCTION: Natural aging of skin tissues, the addition of the cumulative action of the time and radiation exposure result in skin atrophy, wrinkles and degeneration of the extracellular matrix (ECM). The aim of the study was to investigate the beneficial effect of a combination containing retinaldehyde (RAL), delta-tocopherol glucoside (delta-TC) and glycylglycine ole-amide (GGO) and of a dermocosmetic containing the combination. MATERIALS AND METHODS: The protective effect of the combination was assessed through in vitro gene expression of ultraviolet (UV)-irradiated fibroblasts...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28199967/pre-clinical-evaluation-of-small-molecule-loxl2-inhibitors-in-breast-cancer
#4
Joan Chang, Morghan C Lucas, Lidia E Leonte, Marc Garcia-Montolio, Lukram Babloo Singh, Alison D Findlay, Mandar Deodhar, Jonathan S Foot, Wolfgang Jarolimek, Paul Timpson, Janine T Erler, Thomas R Cox
Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases is known to be important in normal tissue development and homeostasis, as well as the onset and progression of solid tumors. Here we tested the anti-tumor properties of two generations of novel small molecule LOXL2 inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumor angiogenesis...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28196225/blood-vessel-basement-membrane-alterations-in-human-retinal-microaneurysms-during-aging
#5
Mariana López-Luppo, Victor Nacher, David Ramos, Joana Catita, Marc Navarro, Ana Carretero, Alfonso Rodriguez-Baeza, Luísa Mendes-Jorge, Jesús Ruberte
Purpose: Microaneurysms, considered a hallmark of retinal vascular disease, are present in aged retinas. Here, the basement membrane of human retinal microaneurysms has been analyzed during aging. Methods: Retinas were obtained from 17 nondiabetic donors. Whole mount retinas and paraffin sections were marked immunohistochemically with antibodies against the main components of the blood basement membrane. Trypsin digestion and transmission electron microscopy also were performed...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28186202/inhibition-of-receptor-interacting-protein-kinase-1-with-necrostatin-1s-ameliorates-disease-progression-in-elastase-induced-mouse-abdominal-aortic-aneurysm-model
#6
Qiwei Wang, Ting Zhou, Zhenjie Liu, Jun Ren, Noel Phan, Kartik Gupta, Danielle M Stewart, Stephanie Morgan, Carmel Assa, K Craig Kent, Bo Liu
Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s)...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157237/mechanisms-underlying-the-cardiac-antifibrotic-effects-of-losartan-metabolites
#7
José Luis Miguel-Carrasco, Javier Beaumont, Gorka San José, María U Moreno, Begoña López, Arantxa González, Guillermo Zalba, Javier Díez, Ana Fortuño, Susana Ravassa
Excessive myocardial collagen deposition and cross-linking (CCL), a process regulated by lysyl oxidase (LOX), determines left ventricular (LV) stiffness and dysfunction. The angiotensin II antagonist losartan, metabolized to the EXP3179 and EXP3174 metabolites, reduces myocardial fibrosis and LV stiffness in hypertensive patients. Our aim was to investigate the differential influence of losartan metabolites on myocardial LOX and CCL in an experimental model of hypertension with myocardial fibrosis, and whether EXP3179 and EXP3174 modify LOX expression and activity in fibroblasts...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143503/genetic-polymorphisms-in-key-hypoxia-regulated-downstream-molecules-and-phenotypic-correlation-in-prostate-cancer
#8
Avelino Fraga, Ricardo Ribeiro, André Coelho, José Ramon Vizcaíno, Helena Coutinho, José Manuel Lopes, Paulo Príncipe, Carlos Lobato, Carlos Lopes, Rui Medeiros
BACKGROUND: In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms. METHODS: Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray...
January 31, 2017: BMC Urology
https://www.readbyqxmd.com/read/28125844/proteomic-analysis-of-the-bovine-and-human-ciliary-zonule
#9
Alicia De Maria, Phillip A Wilmarth, Larry L David, Steven Bassnett
Purpose: The zonule of Zinn (ciliary zonule) is a system of fibers that centers the crystalline lens on the optical axis of the eye. Mutations in zonule components underlie syndromic conditions associated with a broad range of ocular pathologies, including microspherophakia and ectopia lentis. Here, we used HPLC-mass spectrometry to determine the molecular composition of the zonule. Methods: Tryptic digests of human and bovine zonular samples were analyzed by HPLC-mass spectrometry...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28116994/expression-of-lysyl-oxidase-predictive-of-distant-metastasis-of-laryngeal-cancer
#10
Yoon Se Lee, Yangsoon Park, Minsu Kwon, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
Objective To investigate the prognostic significance of lysyl oxidase (LOX) expression in laryngeal cancer. Study Design Retrospective chart review and histologic analysis. Setting Tertiary referral academic center. Subjects and Methods Patients (N = 100) underwent surgical treatment for laryngeal cancer and had tissue specimens available. Immunohistochemical staining for LOX was performed on laryngeal cancer tissue microarrays, and the proportion and intensity of staining were evaluated. Patients with LOX scores ≤6 were classified into the low LOX group, while those with scores >6 were classified into the high LOX group...
January 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28112368/loxl3-sv2-a-novel-variant-of-human-lysyl-oxidase-like-3-loxl3-functions-as-an-amine-oxidase
#11
Chankyu Jeong, Youngho Kim
Human lysyl oxidase-like 3 (LOXL3) functions as a copper-dependent amine oxidase toward collagen and elastin. The LOXL3 protein contains four scavenger receptor cysteine-rich (SRCR) domains in the N-terminus in addition to the C-terminal characteristic domains of the lysyl oxidase (LOX) family, such as a copper-binding domain, a cytokine receptor‑like domain and residues for the lysyl-tyrosyl quinone cofactor. Using BLASTN searches, we identified a novel variant of LOXL3 (termed LOXL3-sv2), which lacked the sequences corresponding to exons 4 and 5 of LOXL3...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28110559/comparing-hydrazine-derived-reactive-groups-as-inhibitors-of-quinone-dependent-amine-oxidases
#12
COMPARATIVE STUDY
Ashley A Burke, Elizabeth S Severson, Shreya Mool, Maria J Solares Bucaro, Frederick T Greenaway, Charles E Jakobsche
Lysyl oxidase has emerged as an important enzyme in cancer metastasis. Its activity has been reported to become upregulated in several types of cancer, and blocking its activity has been shown to limit the metastatic potential of various cancers. The small-molecules phenylhydrazine and β-aminopropionitrile are known to inhibit lysyl oxidase; however, issues of stability, toxicity, and poorly defined mechanisms limit their potential use in medical applications. The experiments presented herein evaluate three other families of hydrazine-derived compounds - hydrazides, alkyl hydrazines, and semicarbazides - as irreversible inhibitors of lysyl oxidase including determining the kinetic parameters and comparing the inhibition selectivities for lysyl oxidase against the topaquinone-containing diamine oxidase from lentil seedlings...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28106301/uxt-is-a-lox-pp-interacting-protein-that-modulates-estrogen-receptor-alpha-activity-in-breast-cancer-cells
#13
Nuria Sánchez-Morgan, Kathrin H Kirsch, Philip C Trackman, Gail E Sonenshein
The lysyl oxidase proenzyme propeptide region (LOX-PP) is a tumor suppressor protein whose mechanism of action is not completely understood. Here, the Ubiquitously eXpressed Transcript (UXT) was identified in a yeast two-hybrid assay with LOX-PP as bait and confirmed as a novel LOX-PP associating protein. UXT, a prefoldin-like protein, is ubiquitous in human and mouse. Since UXT modulates androgen receptor transcriptional activity in prostate cancer, we studied its role in breast cancer. Breast tumors and derived cell lines overexpressed UXT...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28091585/microrna-19b-is-a-potential-biomarker-of-increased-myocardial-collagen-cross-linking-in-patients-with-aortic-stenosis-and-heart-failure
#14
Javier Beaumont, Begoña López, Susana Ravassa, Nerea Hermida, Gorka San José, Idoia Gallego, Félix Valencia, Juan José Gómez-Doblas, Eduardo de Teresa, Javier Díez, Arantxa González
This study analyzed the potential associations of 7 myocardial fibrosis-related microRNAs with the quality of the collagen network (e.g., the degree of collagen fibril cross-linking or CCL) and the enzyme lysyl oxidase (LOX) responsible for CCL in 28 patients with severe aortic stenosis (AS) of whom 46% had a diagnosis of chronic heart failure (HF). MicroRNA expression was analyzed in myocardial and blood samples. From the studied microRNAs only miR-19b presented a direct correlation (p < 0.05) between serum and myocardium...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087451/in-depth-comparative-analysis-of-the-chicken-eggshell-membrane-proteome
#15
Tamer A E Ahmed, Henri-Pierre Suso, Maxwell T Hincke
: The avian eggshell membrane (ESM) is stabilized by extensive cross-linkages, making the identification of its protein constituents technically challenging. Herein, we applied various extraction/solubilization conditions followed by proteomic analysis to characterize the protein constituents of ESM derived from the unfertilized chicken eggs. The egg white and eggshell proteomes (including previous published work) were determined and compared to ESM to identify proteins that are relatively or highly specific to ESM...
January 10, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28077158/ccl2-driven-inflammation-increases-mammary-gland-stromal-density-and-cancer-susceptibility-in-a-transgenic-mouse-model
#16
Xuan Sun, Danielle J Glynn, Leigh J Hodson, Cecilia Huo, Kara Britt, Erik W Thompson, Lucy Woolford, Andreas Evdokiou, Jeffrey W Pollard, Sarah A Robertson, Wendy V Ingman
BACKGROUND: Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. METHODS: Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter...
January 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28073888/selective-targeting-of-lysyl-oxidase-like-2-loxl2-suppresses-hepatic-fibrosis-progression-and-accelerates-its-reversal
#17
Naoki Ikenaga, Zhen-Wei Peng, Kahini A Vaid, Susan B Liu, Shuhei Yoshida, Deanna Y Sverdlov, Amanda Mikels-Vigdal, Victoria Smith, Detlef Schuppan, Yury V Popov
BACKGROUND/AIMS: We studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, and the therapeutic efficacy of a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal in mice. METHODS: Anti-LOXL2 antibody, control antilysyl oxidase antibody or placebo was administered during thioacetamide (TAA)-induced fibrosis progression or during recovery. Therapeutic efficacy in biliary fibrosis was tested in BALB/c...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28065600/lysyl-oxidase-3-is-a-dual-specificity-enzyme-involved-in-stat3-deacetylation-and-deacetylimination-modulation
#18
Li Ma, Chao Huang, Xiong-Jun Wang, Dazhuan Eric Xin, Li-Shun Wang, Quanli C Zou, Ya-Nan S Zhang, Min-Dian Tan, Yu-Mei Wang, Ting C Zhao, Devasis Chatterjee, Rachel A Altura, Chuangui Wang, Yan S Xu, Jing-Hua Yang, Yong-Sheng Fan, Bao-Hui Han, Jianmin Si, Xiaoren Zhang, Jinke Cheng, Zhijie Chang, Y Eugene Chin
In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28060764/loxl4-knockdown-enhances-tumor-growth-and-lung-metastasis-through-collagen-dependent-extracellular-matrix-changes-in-triple-negative-breast-cancer
#19
Sul Ki Choi, Hoe Suk Kim, Tiefeng Jin, Woo Kyung Moon
Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels...
2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28056723/chronic-treatment-with-minoxidil-induces-elastic-fiber-neosynthesis-and-functional-improvement-in-the-aorta-of-aged-mice
#20
Marion Coquand-Gandit, Marie Paule Jacob, Wassim Fhayli, Beatriz Romero Ruiz de la Hermosa, Miglena Georgieva, Stéphanie Bouillot, Eric Estève, Jean-Pierre Andrieu, Sandrine Brasseur, Sophie Bouyon, Natalio Garcia-Honduvilla, Philippe Huber, Julia Bujan, Milena Atanasova, Gilles Faury
Normal arterial aging processes involve vascular cell dysfunction associated with wall stiffening, the latter being due to progressive elastin and elastic fiber degradation, as well as elastin and collagen cross-linking by advanced glycation end-products (AGE). These processes progressively lead to cardiovascular dysfunction during aging. Elastin is only synthesized during late gestation and childhood, and further degradation occurring throughout adulthood cannot be physiologically compensated by replacement of altered material...
January 5, 2017: Rejuvenation Research
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