scholarly journals Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation: Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Marwa Kamel ◽  
Mohamed Wagih ◽  
Gokhan S. Kilic ◽  
Concepcion R. Diaz-Arrastia ◽  
Mohamed A. Baraka ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Treatment Options ◽  
Uterine Fibroids ◽  
Cross Linking ◽  
Ki 67 ◽  
Subsequent Formation ◽  
Lysyl Oxidases ◽  
Cross Links ◽  
Collagen Cross Linking

The role of the extracellular matrix (ECM) in uterine fibroids (UF) has recently been appreciated. Overhydroxylation of lysine residues and the subsequent formation of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links underlie the ECM stiffness and profoundly affect tumor progression. The aim of the current study was to investigate the relationship between ECM of UF, collagen and collagen cross-linking enzymes [lysyl hydroxylases (LH) and lysyl oxidases (LOX)], and the development and progression of UF. Our results indicated that hydroxyl lysine (Hyl) and HP cross-links are significantly higher in UF compared to the normal myometrial tissues accompanied by increased expression of LH (LH2b) and LOX. Also, increased resistance to matrix metalloproteinases (MMP) proteolytic degradation activity was observed. Furthermore, the extent of collagen cross-links was positively correlated with the expression of myofibroblast marker (α-SMA), growth-promoting markers (PCNA; pERK1/2;FAKpY397; Ki-67; and Cyclin D1), and the size of UF. In conclusion, our study defines the role of overhydroxylation of collagen and collagen cross-linking enzymes in modulating UF cell proliferation, differentiation, and resistance to MMP. These effects can establish microenvironment conducive for UF progression and thus represent potential target treatment options of UF.

scholarly journals Repair Kinetics of Genomic Interstrand DNA Cross-Links: Evidence for DNA Double-Strand Break-Dependent Activation of the Fanconi Anemia/BRCA Pathway

2004 ◽  
Vol 24 (1) ◽  
pp. 123-134 ◽  
Author(s):  
Andreas Rothfuss ◽  
Markus Grompe
Keyword(s):  
Fanconi Anemia ◽  
Strand Break ◽  
S Phase ◽  
Dna Double Strand Breaks ◽  
Subsequent Formation ◽  
Strand Breaks ◽  
Dna Double Strand Break ◽  
Cross Links ◽  
Kinetics Of

ABSTRACT The detailed mechanisms of DNA interstrand cross-link (ICL) repair and the involvement of the Fanconi anemia (FA)/BRCA pathway in this process are not known. Present models suggest that recognition and repair of ICL in human cells occur primarily during the S phase. Here we provide evidence for a refined model in which ICLs are recognized and are rapidly incised by ERCC1/XPF independent of DNA replication. However, the incised ICLs are then processed further and DNA double-strand breaks (DSB) form exclusively in the S phase. FA cells are fully proficient in the sensing and incision of ICL as well as in the subsequent formation of DSB, suggesting a role of the FA/BRCA pathway downstream in ICL repair. In fact, activation of FANCD2 occurs slowly after ICL treatment and correlates with the appearance of DSB in the S phase. In contrast, activation is rapid after ionizing radiation, indicating that the FA/BRCA pathway is specifically activated upon DSB formation. Furthermore, the formation of FANCD2 foci is restricted to a subpopulation of cells, which can be labeled by bromodeoxyuridine incorporation. We therefore conclude that the FA/BRCA pathway, while being dispensable for the early events in ICL repair, is activated in S-phase cells after DSB have formed.

scholarly journals Thyrotropin cross-links to the thyrotropin receptor through both the α and β subunits

1986 ◽  
Vol 235 (3) ◽  
pp. 879-882 ◽  
Author(s):  
P R Buckland ◽  
C R Rickards ◽  
R D Howells ◽  
B R Smith
Keyword(s):  
Tsh Receptor ◽  
Alpha Subunit ◽  
Receptor Interaction ◽  
Cross Linking ◽  
Thyrotropin Receptor ◽  
Cross Link ◽  
Receptor Binding Site ◽  
Form Part ◽  
Cross Links

We have recently shown that the beta subunit of thyrotropin (TSH) can be cross-linked to the TSH receptor [Buckland, Strickland, Pierce & Rees Smith (1985) Endocrinology (Baltimore) 116, 2122-2124; Buckland, Strickland & Rees Smith (1985) Biochem. Soc. Trans. 13, 942-943]. We failed, however, to cross-link the alpha subunit to the receptor, leaving the role of this subunit in the TSH-TSH-receptor interaction uncertain. We now report the successful cross-linking of the TSH alpha subunit to the receptor by the use of two different cross-linking reagents. Our studies suggest therefore that both subunits of TSH form part of the hormone's receptor-binding site.

Failure of mineralized collagen fibrils: Modeling the role of collagen cross-linking

2008 ◽  
Vol 41 (7) ◽  
pp. 1427-1435 ◽  
Author(s):  
Thomas Siegmund ◽  
Matthew R. Allen ◽  
David B. Burr
Keyword(s):  
Collagen Fibrils ◽  
Cross Linking ◽  
Collagen Cross Linking ◽  
Mineralized Collagen

scholarly journals Chemistry of collagen cross-linking: biochemical changes in collagen during the partial mineralization of turkey leg tendon

1997 ◽  
Vol 322 (2) ◽  
pp. 535-542 ◽  
Author(s):  
Lynda KNOTT ◽  
John F. TARLTON ◽  
Allen J. BAILEY
Keyword(s):  
Collagen Matrix ◽  
Cross Linking ◽  
Cross Link ◽  
Lysine Residues ◽  
Collagen Mineralization ◽  
Cross Links ◽  
The Cross ◽  
Calcified Tissues ◽  
Turkey Leg Tendon ◽  
Collagen Cross Linking

With age, the proximal sections of turkey leg tendons become calcified, and this phenomenon has led to their use as a model for collagen mineralization. Mineralizing turkey leg tendon was used in this study to characterize further the composition and cross-linking of collagen in calcified tissues. The cross-link profiles of mineralizing collagen are significantly different from those of other collagenous matrices with characteristically low amounts of hydroxylysyl-pyridinoline and the presence of lysyl-pyridinoline and pyrrolic cross-links. However, the presence of the immature cross-link precursors previously reported in calcifying tissues was not supported in the present study, and was found to be due to the decalcification procedure using EDTA. Analysis of tendons from young birds demonstrated differences in the cross-link profile which indicated a higher level of hydroxylation of specific triple-helical lysines involved in cross-linking of the proximal tendon. This may be related to later calcification, suggesting that this part of the tendon is predestined to be calcified. The minimal changes in lysyl hydroxylation in both regions of the tendon with age were in contrast with the large changes in the cross-link profile, indicating differential hydroxylation of the helical and telopeptide lysine residues. Changes with age in the collagen matrix, its turnover and thermal properties in both the proximal and distal sections of the tendon clearly demonstrate that a new and modified matrix is formed throughout the tendon, and that a different type of matrix is formed at each site.

scholarly journals Corneal Cross-linking can halt the Progression of Keratoconus, but what is the Best Approach to Treatment?

2015 ◽  
Vol 4 (2) ◽  
pp. 47-51 ◽  
Author(s):  
Frederik Raiskup ◽  
Mark Hillen
Keyword(s):  
Adverse Events ◽  
Ultraviolet Light ◽  
Corneal Epithelium ◽  
Treatment Options ◽  
Cross Linking ◽  
Light Illumination ◽  
Corneal Crosslinking ◽  
Number Of Treatment ◽  
Collagen Cross Linking ◽  
Corneal Collagen

ABSTRACT There are a number of treatment options for keratoconus, but only corneal collagen cross-linking (CXL) appears to halt the progression of the disease. To guarantee effective cross-linking, CXL treatment involves removal of the corneal epithelium prior to riboflavin application and ultraviolet light illumination to ensure that riboflavin reaches the collagen in the stroma—epithelial-on cross-linking (‘Epi-off’ CXL). Several methods of ‘Epi-on’ (transepithelial) CXL have been proposed, as keeping the corneal epithelium intact should be less painful and help avoid other CXL-associated adverse events. The evidence to date is that Epi-off CXL remains the most effective method of strengthening the cornea and slowing keratoconus progression—but transepithelial methods are gaining ground. How to cite this article Raiskup F, Hillen M. Corneal Crosslinking can halt the Progression of Keratoconus, but what is the Best Approach to Treatment? Int J Kerat Ect Cor Dis 2015; 4(2):47-51.

scholarly journals ROLE OF CORNEAL COLLAGEN CROSS LINKING IN KERATOCONUS

2015 ◽  
Vol 4 (73) ◽  
pp. 12760-12774
Author(s):  
Atul Gupta ◽  
Superna M ◽  
Bhimasankar D ◽  
Vijayleela M
Keyword(s):  
Cross Linking ◽  
Collagen Cross Linking ◽  
Corneal Collagen

Collagen cross-linking mediated by lysyl hydroxylase 2: an enzymatic battlefield to combat fibrosis

2019 ◽  
Vol 63 (3) ◽  
pp. 377-387 ◽  
Author(s):  
Bram Piersma ◽  
Ruud A. Bank
Keyword(s):  
Organ Failure ◽  
Molecular Basis ◽  
Repair Process ◽  
Cross Linking ◽  
Collagen Network ◽  
Lysyl Hydroxylase ◽  
Cross Links ◽  
Collagen Cross Linking ◽  
Excessive Accumulation

Abstract The hallmark of fibrosis is an excessive accumulation of collagen, ultimately leading to organ failure. It has become evident that the deposited collagen also exhibits qualitative modifications. A marked modification is the increased cross-linking, leading to a stabilization of the collagen network and limiting fibrosis reversibility. Not only the level of cross-linking is increased, but also the composition of cross-linking is altered: an increase is seen in hydroxyallysine-derived cross-links at the expense of allysine cross-links. This results in irreversible fibrosis, as collagen cross-linked by hydroxyallysine is more difficult to degrade. Hydroxyallysine is derived from a hydroxylysine in the telopeptides of collagen. The expression of lysyl hydroxylase (LH) 2 (LH2), the enzyme responsible for the formation of telopeptidyl hydroxylysine, is universally up-regulated in fibrosis. It is expected that inhibition of this enzyme will lead to reversible fibrosis without interfering with the normal repair process. In this review, we discuss the molecular basis of collagen modifications and cross-linking, with an emphasis on LH2-mediated hydroxyallysine cross-links, and their implications for the pathogenesis and treatment of fibrosis.

scholarly journals The Role of Nonenzymatic Glycation and Carbonyls in Collagen Cross-Linking for the Treatment of Keratoconus

2011 ◽  
Vol 52 (9) ◽  
pp. 6363 ◽  
Author(s):  
Gage Brummer ◽  
Stacy Littlechild ◽  
Scott McCall ◽  
Yuntao Zhang ◽  
Gary W. Conrad
Keyword(s):  
Cross Linking ◽  
Nonenzymatic Glycation ◽  
Collagen Cross Linking
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