Tissue-Specific Effects of Aldose Reductase Inhibition on Fluorescence and Cross-Linking of Extracellular Matrix in Chronic Galactosemia: Relationship to Pentosidine Cross-Links

Diabetes ◽  
1991 ◽  
Vol 40 (8) ◽  
pp. 1049-1056 ◽  
Author(s):  
S. Richard ◽  
C. Tamas ◽  
D. R. Sell ◽  
V. M. Monnier
Keyword(s):  
Extracellular Matrix ◽  
Aldose Reductase ◽  
Cross Linking ◽  
Tissue Specific ◽  
Aldose Reductase Inhibition ◽  
Specific Effects ◽  
Cross Links

Lysyl oxidases: from enzyme activity to extracellular matrix cross-links

2019 ◽  
Vol 63 (3) ◽  
pp. 349-364 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Sylvie Ricard-Blum
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Catalytic Domain ◽  
Lysyl Oxidase ◽  
Dimensional Structure ◽  
Cross Linking ◽  
Copper Binding ◽  
Molecular Features ◽  
Ecm Proteins ◽  
Cross Links

Abstract The lysyl oxidase family comprises five members in mammals, lysyl oxidase (LOX) and four lysyl oxidase like proteins (LOXL1-4). They are copper amine oxidases with a highly conserved catalytic domain, a lysine tyrosylquinone cofactor, and a conserved copper-binding site. They catalyze the first step of the covalent cross-linking of the extracellular matrix (ECM) proteins collagens and elastin, which contribute to ECM stiffness and mechanical properties. The role of LOX and LOXL2 in fibrosis, tumorigenesis, and metastasis, including changes in their expression level and their regulation of cell signaling pathways, have been extensively reviewed, and both enzymes have been identified as therapeutic targets. We review here the molecular features and three-dimensional structure/models of LOX and LOXLs, their role in ECM cross-linking, and the regulation of their cross-linking activity by ECM proteins, proteoglycans, and by inhibitors. We also make an overview of the major ECM cross-links, because they are the ultimate molecular readouts of LOX/LOXL activity in tissues. The recent 3D model of LOX, which recapitulates its known structural and biochemical features, will be useful to decipher the molecular mechanisms of LOX interaction with its various substrates, and to design substrate-specific inhibitors, which are potential antifibrotic and antitumor drugs.

scholarly journals Cross-linking reveals laminin coiled-coil architecture

2016 ◽  
Vol 113 (47) ◽  
pp. 13384-13389 ◽  
Author(s):  
Gad Armony ◽  
Etai Jacob ◽  
Toot Moran ◽  
Yishai Levin ◽  
Tevie Mehlman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Self Assembly ◽  
Quaternary Structure ◽  
Coiled Coil ◽  
Surface Proteins ◽  
Cross Linking ◽  
Single Particle Reconstruction ◽  
Cross Links ◽  
Particle Reconstruction ◽  
Key Questions

Laminin, an ∼800-kDa heterotrimeric protein, is a major functional component of the extracellular matrix, contributing to tissue development and maintenance. The unique architecture of laminin is not currently amenable to determination at high resolution, as its flexible and narrow segments complicate both crystallization and single-particle reconstruction by electron microscopy. Therefore, we used cross-linking and MS, evaluated using computational methods, to address key questions regarding laminin quaternary structure. This approach was particularly well suited to the ∼750-Å coiled coil that mediates trimer assembly, and our results support revision of the subunit order typically presented in laminin schematics. Furthermore, information on the subunit register in the coiled coil and cross-links to downstream domains provide insights into the self-assembly required for interaction with other extracellular matrix and cell surface proteins.

scholarly journals Tissue-Specific Effects of Esophageal Extracellular Matrix

2015 ◽  
Vol 21 (17-18) ◽  
pp. 2293-2300 ◽  
Author(s):  
Timothy J. Keane ◽  
Aaron DeWard ◽  
Ricardo Londono ◽  
Lindsey T. Saldin ◽  
Arthur A. Castleton ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tissue Specific ◽  
Specific Effects

The effect of chronic treadmill exercise and acetaminophen on collagen and cross-linking in rat skeletal muscle and heart

2015 ◽  
Vol 308 (4) ◽  
pp. R294-R299 ◽  
Author(s):  
Chad C. Carroll ◽  
Karl Martineau ◽  
Kathryn A. Arthur ◽  
Richard T. Huynh ◽  
Brent D. Volper ◽  
...  
Keyword(s):  
Gastrocnemius Muscle ◽  
Treadmill Exercise ◽  
Dry Weight ◽  
Collagen Content ◽  
Cross Linking ◽  
Rat Skeletal Muscle ◽  
Oral Gavage ◽  
Specific Effects ◽  
Male Wistar Rats ◽  
Cross Links

The purpose of this study was to determine whether exercise and/or acetaminophen (APAP) alter collagen and cross-linking in the rat gastrocnemius muscle, soleus muscle, and heart. Male Wistar rats ( n = 50; 8 wk old) were divided into placebo (PLA) or APAP groups and sedentary (SED) or exercised (RUN) groups. APAP (200 mg/kg) was administered daily by oral gavage. Exercised groups ran on a treadmill 5 days/wk for 8 wk with progression to 60 min/day, 20 m/min, and 8° incline. Tissues were assayed for collagen (hydroxyproline) and hydroxylyslpyridinoline (HP) and lysylpyridinoline (LP) cross-links by HPLC. Collagen content (μg/mg dry weight) was greater in both the gastrocnemius (SED-PLA: 114 ± 16 vs. RUN-PLA: 244 ± 32; P < 0.001) and soleus (SED-PLA: 51 ± 7 vs. RUN-PLA: 99 ± 27; P = 0.005) of exercised animals. In contrast, collagen content was not significantly greater in exercised animals treated with APAP (SED-APAP: 113 ± 16 vs. RUN-APAP: 145 ± 21) and soleus (SED-APAP: 55 ± 8 vs. RUN-APAP: 57 ± 10). HP cross-linking (mmol/mol collagen) in the gastrocnemius (SED-PLA: 126 ± 28, RUN-PLA: 50 ± 7, SED-APAP: 41 ± 7, and RUN-APAP: 30 ± 4) and soleus muscles (SED-PLA: 547 ± 107, RUN-PLA: 318 ± 92, SED-APAP: 247 ± 64, and RUN-APAP: 120 ± 17) was lower in exercised rats compared with sedentary rats ( P < 0.05). Cross-linking was further reduced in animals treated with APAP ( P < 0.05). Neither heart collagen nor cross-linking was influenced by exercise or APAP ( P > 0.05). Our findings suggest that exercise and APAP have tissue-specific effects on muscle collagen. Given the widespread use of APAP as an analgesic and antipyretic, further work in humans is warranted.

scholarly journals TGFβ-1 Induced Cross-Linking of the Extracellular Matrix of Primary Human Dermal Fibroblasts

2021 ◽  
Vol 22 (3) ◽  
pp. 984
Author(s):  
Mariya E. Semkova ◽  
J. Justin Hsuan
Keyword(s):  
Extracellular Matrix ◽  
Lysyl Oxidase ◽  
Transglutaminase 2 ◽  
Dermal Fibroblasts ◽  
Cross Linking ◽  
Human Dermal Fibroblasts ◽  
Tgfβ Signalling ◽  
A Cell ◽  
Cross Links

Excessive cross-linking is a major factor in the resistance to the remodelling of the extracellular matrix (ECM) during fibrotic progression. The role of TGFβ signalling in impairing ECM remodelling has been demonstrated in various fibrotic models. We hypothesised that increased ECM cross-linking by TGFβ contributes to skin fibrosis in Systemic Sclerosis (SSc). Proteomics was used to identify cross-linking enzymes in the ECM of primary human dermal fibroblasts, and to compare their levels following treatment with TGFβ-1. A significant upregulation and enrichment of lysyl-oxidase-like 1, 2 and 4 and transglutaminase 2 were found. Western blotting confirmed the upregulation of lysyl hydroxylase 2 in the ECM. Increased transglutaminase activity in TGFβ-1 treated ECM was revealed from a cell-based assay. We employed a mass spectrometry-based method to identify alterations in the ECM cross-linking pattern caused by TGFβ-1. Cross-linking sites were identified in collagens I and V, fibrinogen and fibronectin. One cross-linking site in fibrinogen alpha was found only in TGFβ-treated samples. In conclusion, we have mapped novel cross-links between ECM proteins and demonstrated that activation of TGFβ signalling in cultured dermal fibroblasts upregulates multiple cross-linking enzymes in the ECM.

Reduction of glomerular hyperfiltration in normoalbuminuric IDDM patients by 6 mo of aldose reductase inhibition

Diabetes ◽  
1991 ◽  
Vol 40 (5) ◽  
pp. 527-531 ◽  
Author(s):  
M. M. Pedersen ◽  
J. S. Christiansen ◽  
C. E. Mogensen
Keyword(s):  
Aldose Reductase ◽  
Glomerular Hyperfiltration ◽  
Aldose Reductase Inhibition
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