Mechanisms and consequences of oxidative damage to extracellular matrix

Abstract

Considerable evidence exists for oxidative damage to extracellular materials during multiple human pathologies. Unlike cells, the extracellular compartment of most biological tissues is less well protected against oxidation than intracellular sites in terms of the presence of both antioxidants (low molecular mass and enzymatic) and repair enzymes. The extracellular compartment may therefore be subject to greater oxidative stress, marked alterations in redox balance and an accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to ECM (extracellular matrix) are poorly understood, despite the growing realization that changes in matrix structure not only have structural consequences, but also play a key role in the regulation of cellular adhesion, proliferation, migration and cell signalling. The ECM also plays a key role in cytokine and growth factor binding, and matrix modifications would therefore be expected to alter these parameters. In the present study, we review mechanisms of oxidative damage to ECM, resulting changes in matrix structure and how this affects cellular behaviour. The role of such damage in the development and progression of inflammatory diseases is also discussed with particular reference to cardiovascular disease.

Oxidised protein metabolism: recent insights

“…There is evidence that the extracellular compartment in many biological tissues is poorly equipped with antioxidants compared to the intracellular domain and this, coupled with a high number of long-lived proteins, can result in the accumulation of oxidised proteins within the ECM (Kennett et al, 2011;Chuang et al, 2014). Much of the more recent work in this area has been performed in the context of ageing and often specifically in relation to skin ageing.…”

“…Extracellular matrix (ECM) proteins such as collagen and elastin as well as ECM glycoproteins and proteoglycans are also subject to oxidative modifications from oxidants generated on the plasma membrane or extracellularly (Kennett et al, 2011;Chuang et al, 2014). There is evidence that the extracellular compartment in many biological tissues is poorly equipped with antioxidants compared to the intracellular domain and this, coupled with a high number of long-lived proteins, can result in the accumulation of oxidised proteins within the ECM (Kennett et al, 2011;Chuang et al, 2014).…”

“…Oxidative damage to skin can also result in increased activity of elastases and collagenases due to activation of macrophages, neutrophils and fibroblasts resulting in a faster turnover of these ECM proteins (Kammeyer and Luiten, 2015). ECM oxidation can have a profound effect on cell behaviour and can influence factors such as adhesion, proliferation and can stimulate the release of a range of proteolytic enzymes (Kennett et al, 2011). Repetitive irradiation with UVB resulted in loss of the GAG hyaluronic acid (HA) from murine dermis (Dai et al, 2007).…”

In-vivo evaluation of apocynin for prevention of Helicobacter pylori-induced gastric carcinogenesis

“…This is the case for H. pylori-induced gastric inflammation, but also for disease caused by Mycobacterium tuberculosis (Eruslanov et al, 2005). Localized treatment with apocynin could prevent the generation of extracellular release of ROS and an important part of the associated tissue damage (Kennett et al, 2011).…”

Biomechanical Behavior of Atherosclerotic Plaque

“…Protein oxidation can also lead to cross-linking between protein molecules (Stadtman 2006). Since the ECM lacks many inactivating enzymes and antioxidants that protect cellular regions of tissue, the ECM may be particularly susceptible to oxidative damage during aging compared to cellular regions (Kennett et al 2011).…”