Temporal development of near-native functional properties and correlations with qMRI in self-assembling fibrocartilage treated with exogenous lysyl oxidase
As part of this we explored the addition of an inhibitor of the collagen crosslinking enzyme lysyl oxidase
[beta]-APN to see to what extent this might reduce the cell induced contraction of these grafts in vitro.
Li, "Lysyl oxidase
: properties, specificity, and biological roles inside and outside of the cell," Journal of Cellular Biochemistry, vol.
Immunohistochemical localization of lysyl oxidase
in normal human skin.
The lysyl oxidase
(LOX) family, which is composed of five enzymes (LOX and LOXL1/2/3/4), catalyzes oxidative deamination of lysine residues in their protein substrates, generating highly reactive aldehyde residues that initiate inter- and intramolecular cross-linkages .
The formation of fibrosis correlates with new collagen deposition and TGF-beta-induced myofibroblast differentiation, as well as elastin gene expression, WNT-1 inducible signaling pathway protein-1, lysyl oxidase
, and type V collagen gene expression (as discussed in ).
BAPN is a compound known to cause lathyrism, a neurological disease by inhibiting lysyl oxidase
, the enzyme that initiates cross-linkage formation in elastin and collagen; this action prevents the formation of cross-bonds, strictures, and collagen synthesis .
This reaction is catalyzed by lysyl oxidase
(LOX1), a Cu dependent enzyme (Siegel et al., 1970; Harris, 1976).
Copper is also required for the activity of lysyl oxidase
, an enzyme required for the cross-linking of collagen and elastin.
Some of the mechanisms responsible for this reduction are increased elastase activity,6 decreased serum elastase inhibitor level, decreased elastin gene expression, abnormal copper metabolism/copper deficiency and low lysyl oxidase
For example, expression of the hypoxia-regulated gene LOX (lysyl oxidase
) predicts relapse in human breast tumors (28), but recent studies suggest that systemic secretion of lysyl oxidase
into the lung and liver might facilitate the homing of disseminated cancer cells to these organs through the formation of a prometastatic microenvironment (29).
The enzyme called lysyl oxidase
(LOX) has been found to stiffen collagen, a major component of the supportive tissue in the breast.