A. Chronopoulos

A. Tang

Boyd-White

Brownlee

Buckingham

Cardoso

Chavers

Csiszar

E. Beglova

Erler

Gilad

Gorogh

Grant

Hayashi

Hollosi

Hurtado

Kagan

Kirschmann

Le Pape

Ljubimov

Lucero

Merimee

Ortolan

Oshitari

P. C. Trackman

Palamakumbura

Paszek

Payne

Rodriguez

Roth

S. Roy

Trackman

Tr  eb

Tsilibary

Vadasz

Vinores

Walton

Wilmarth

English

PubMed


                  OBJECTIVE
                  In diabetes, retinal vascular basement membrane (BM) undergoes significant thickening and compromises vessel function including increased vascular permeability, a prominent lesion of early diabetic retinopathy. In this study we determined whether altered expression and activity of lysyl oxidase (LOX), a cross-linking enzyme, may compromise vascular basement membrane functional integrity under high-glucose (HG) conditions.
               
               
                  RESEARCH DESIGN AND METHODS
                  Rat retinal endothelial cells (RRECs) grown in normal (5 mmol/l) or HG (30 mmol/l glucose) medium for 7 days were assessed for expression of LOX and proLOX by Western blot analysis and LOX enzyme activity. To determine whether HG alters cellular distribution patterns of LOX and proLOX, immunostaining with respective antibodies was performed. Similarly, cells grown in normal or HG medium were subjected to both LOX inhibition with β-aminopropionitrile (BAPN) and by small interfering RNA knockdown, and respectively examined for cell monolayer permeability. Additionally, retinas of streptozotocin (STZ)-induced diabetic rats were analyzed to determine if diabetes altered LOX expression.
               
               
                  RESULTS
                  Western blot analysis revealed significantly increased LOX and proLOX expression in cells grown in HG medium compared with those grown in normal medium. The increased LOX level was strikingly similar to LOX upegulation in the diabetic retinas. In cells grown in HG medium, LOX activity and cell monolayer permeability was significantly increased, as were LOX and proLOX immunostaining. Small interfering RNA- or BAPN–induced-specific blockage of LOX expression or activity, respectively, reduced cell monolayer permeability.
               
               
                  CONCLUSIONS
                  HG-induced increased LOX expression and activity compromises barrier functional integrity, a prominent lesion of diabetic retinopathy.
               </jats:sec

Argyrios Chronopoulos

Amanda Tang

Ekaterina Beglova

Philip C. Trackman

Sayon Roy

Crossref

Diabetes

High Glucose Increases Lysyl Oxidase Expression and Activity in Retinal Endothelial Cells: Mechanism for Compromised Extracellular Matrix Barrier Function

A loss-of-function polymorphism in the propeptide domain of the LOX gene and breast cancer.

A molecular role for lysyl oxidase in breast cancer invasion.

Abnormal deposition of collagen around hepatocytes in Wilson’s disease is associated with hepatocyte speciﬁc expression of lysyl oxidase and lysyl oxidase like protein-2.

Basement membrane abnormalities in human eyes with diabetic retinopathy.

Cellular mechanisms of blood-retinal barrier dysfunction in macular edema. Doc Ophthalmol

Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: changes in the expression of LOXL during development and growth of mouse tissues.

Developmental roles of the BMP1/TLD metalloproteinases.

Effect of combined antisense oligonucleotides against high-glucose- and diabetes-induced overexpression of extracellular matrix components and increased vascular permeability.

Effect of cross-linking on matrix permeability. A model for AGE-modiﬁed basement membranes Diabetes 1996;45:

Electron microscopic investigation of the effects of diabetes mellitus on the Achilles tendon. J Foot Ankle Surg 1997;36:272–278; discussion 330

Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer’s disease brain.

Expression and puriﬁcation of enzymatically active forms of the human lysyl oxidase-like protein 4.

Fibronectin overexpression in retinal microvessels of patients with diabetes.

Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability.

Glucose-induced Akt1 activation mediates ﬁbronectin synthesis in endothelial cells.

Glycation products and the pathogenesis of diabetic complications. Diabetes Care

Hypoxia promotes ﬁbrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition.

Hypoxia-inducible factor 1 induces ﬁbrosis and insulin resistance in white adipose tissue.

In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles.

Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice.

Increased expression of basement membrane collagen in human diabetic retinopathy.

Integrin overexpression induced by high glucose and by human diabetes: potential pathway to cell dysfunction in diabetic microangiopathy.

Lysyl oxidase as a potential therapeutic target. Drug News Perspect

Lysyl oxidase is essential for hypoxia-induced metastasis.

Lysyl oxidase is required for vascular and diaphragmatic development in mice.

Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling. Oncogene

Lysyl oxidase-like 2 promotes migration in noninvasive breast cancer cells but not in normal breast epithelial cells.

Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1.

Lysyl oxidase: an oxidative enzyme and effector of cell function.

Lysyl oxidase: mechanism, regulation and relationship to liver ﬁbrosis. Pathol Res Pract

Lysyl oxidases: a novel multifunctional amine oxidase family.

Microvascular basement membranes in diabetes mellitus.

Molecular cloning and biological activity of a novel lysyl oxidase-related gene expressed in cartilage.

Molecular regulation of lung development.

morphometric and ultrastructural analysis of anastomotic healing in the intestine of normal and diabetic rats. Exp Clin Endocrinol Diabetes

Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells.

Nonenzymatic glycosylation of basement membrane collagen in diabetes mellitus.

Nonenzymatic glycosylation of collagen in diabetes: incidence on increased normal platelet aggregation. Haemostasis

Paradoxical roles for lysyl oxidases in cancer—a prospect.

Post-translational glycosylation and proteolytic processing of a lysyl oxidase precursor.

Relationship between retinal and glomerular lesions in IDDM patients.

Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus.

Repression of BCL2 by the tumor suppressor activity of the lysyl oxidase propeptide inhibits transformed phenotype of lung and pancreatic cancer cells.

Selective upregulation and ampliﬁ-cation of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma.

Studies of the permeation properties of glomerular basement membrane: cross-linking renders glomerular basement membrane permeable to protein.

Tensional homeostasis and the malignant phenotype.

The lysyl oxidase pro-peptide attenuates ﬁbronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells.

The microangiopathic lesions of diabetes mellitus: an evaluation of possible causative factors. Trans Assoc Am Physicians

The propeptide domain of lysyl oxidase induces phenotypic reversion of ras-transformed cells.

The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer.

Three-dimensional context regulation of metastasis.

Trabecular meshwork cells grown on ﬁlters. Conductivity and cytochalasin effects Invest Ophthalmol Vis Sci

Trackman PC. A ﬂuorometric assay for detection of lysyl oxidase enzyme activity in biological samples. Anal Biochem

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2992778

High Glucose Increases Lysyl Oxidase Expression and Activity in Retinal Endothelial Cells: Mechanism for Compromised Extracellular Matrix Barrier Function

Abstract

Similar works

Full text

Available Versions

Crossref