What are ROS?
ROS, Reactive oxygen species, is a generic term to describe
a range of oxygen containing radicals such as hydroxyl radical OH., superoxide
anion O2-., nitric oxide NO, perhydroxyl radical HO2. and non-radical species
such as hydrogen peroxide H2O2 and hypochlorous acid HOCl. They are formed as
by-products during normal metabolism processes, primarily in mitochondria, but
also as a cellular response to ionising radiations, pollutants, xenobiotics,
cytokine and bacterial invasion.1
Oxidative stress -
When the concentration of ROS becomes harmful
A certain level of ROS is important for several
physiological processes such as wound healing, tissue regeneration and
protection from pathogens.2,3 If the concentration of ROS increases, they will
be scavenged by enzymatic oxidants (for instance such as SOD, catalase, GPx) or
non-enzymatic antioxidants (e.g. vitamin C, vitamin E, transferrin,
beta-carotene). However, when ROS are produced too quickly and cells are no
longer able to quench them by using suitable antioxidant defences, they become
harmful and can cause damage to proteins, lipid molecules of the cell
membranes, carbohydrates as well as RNA and DNA. This is referred to as
oxidative stress i.e. a state where ROS are overproduced and the rate of
clearance via endogenous and exogeneous antioxidants is no longer sufficient to
protect cells and tissues from their toxic effects. The biological consequences
of oxidative stress include for instance aging, when the levels of ROS remain
low but with a gradual increase or cancer when there is a rapid increase in the
production of ROS resulting in a high concentration of ROS.
Oxidative stress
markers
Unfortunately, ROS radicals are extremely reactive with a
short half-life and consequently difficult to use as markers of oxidative
stress. Nevertheless, their reactions with lipids, proteins and DNA lead to the
formation of stable molecules that can be used as secondary markers of oxidative
stress.
1. Protein oxidation: Oxidation of proteins can lead to
fragmentation resulting in the loss of their biological activities and the
formation of residues such as o-tyrosine, di-tyrosine and dibromo-tyrosine that
can be used as markers of oxidative stress.
2. Lipid peroxidation: Polyunsaturated lipid molecules in
cell membranes are highly susceptible to reaction with radicals via a chain
reaction. This leads to the formation of lipid peroxides that can further
decompose into aldehydes such as acrolein, malondialdehyde (MDA), hydroxynonenal
(HNE), 4-hydroxy-2-hexenal (HNN), crotonaldehyde (CRA) and adducts such as hexanoyl-lysine
(HEL) and 7-ketocholesterol (7KC). Common pathological processes linked to MDA
and 4-HNE are Alzheimer’s disease, Parkinson’s disease, cancer, cardiovascular
diseases and diabetes.
3. DNA damage: Oxidation of the nucleic acids can lead to
the formation of 8-hydroxy 2’-deoxyguanosine, 8-OHdG. Increased levels of
8-OHdG is linked to aging as well as several pathological conditions such as
cancer and diabetes and hence represents a useful marker of oxidation stress. 8-OHdG
can be easily quantified using ELISA kits from urine or complex samples such as
plasma, cell lysates and tissues.
Tools for oxidative
stress research
StressMarq has developed an extensive range of products to
study oxidative stress. These products are currently available in the UK and
Ireland through Newmarket Scientific and include:
- DNA damage ELISA kit, quantifying oxidative damage on DNA by measuring 8-OHdG levels
References:
1. Ray PD et al, Cell Signal.
2012; 24 (5):981-990
2. Onodera Y et al, FEBS Open
Bio, 2015; 5: 492–501.
3. Di Meo et al, Oxid Med Cell
Longev. 2016; 2016: 7909186.
Written by Magalie Dale
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