Pan European Networks - Horizon 2020 - page 181

free radicals from them. These reactions are, of course, much
more common in areas of strong sunlight.
Diseases and accumulated oxidative stress
The production of free radical waste products is therefore a
normal process that always occurs in our bodies, i.e. from birth to
death.Why does this not lead to the breakdown and deterioration
of our bodies like the rusting car or the rotting apple? The answer
is that we have a housekeeping machinery consisting of an
intricate system of different molecules that protects us against the
toxic reactions of the waste products. These protection molecules
thus ‘preserve’ our bodies.Without these, we would perhaps not
last more than a few months.
However, sometimes the production of waste products can
increase acutely, for instance during an infection, a trauma, blood
transfusion etc. Other times, the production can increase on a
more long term basis, such as in chronic diseases like diabetes
and rheumatoid arthritis. During these conditions, oxidative stress
is prevailing and contributes to the symptoms of the diseases.
Ageing, according to some scientists in the field, is a result of an
accumulation of unwanted oxidative reactions from a lifetime’s
production of waste products.
Alpha-1-microglobulin – the cleaning protein
Some of the protection molecules are collectively called
‘antioxidants’. Antioxidants use many different methods and they
are produced in different locations around our body. One of the
antioxidants, which is present in all parts of the body, is a small
protein called A1M. This protein belongs to the antioxidation group
of proteins and works by cleaning waste products and repairing
oxidised tissue. A1M was discovered 45 years ago in human urine
and caught immediate interest because of its unusual brown
colour.We know today that the brown colour is the result of
cleaning up and binding waste products. Brown colour is always a
result of strong heterogeneity and thus shows that the substances
bound to A1M represent a mix of hundreds of different molecules.
All vertebrate animals, including fish, birds and humans, have a
version of A1M. In fact, no single individual, man or animal has
been shown to lack the protein, and the concentration of A1M is
kept fairly constant in all the species where it has been measured.
Fig. 1 shows the lifecycle of A1M from the cradle (liver) to the
grave (kidneys). The production and degradation rate of A1M is
rapid and the entire lifecycle of an average A1M molecule is
therefore only around ten minutes. The main part of A1M is
produced in the liver, the largest gland of the body. The protein is
secreted from the liver to the blood and quickly transported to all
organs, where it penetrates across the vessel walls out to the
space around the cells and matrix of the tissues. Although the
liver is responsible for the main production, most other cells can
make a local version of A1M but at a lower rate.
H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
H E A L T H : D I S E A S E R E S E A R C H
Fig. 1 Lifecycle of antioxidation protein A1M (blue) in human tissues. See text for details. Figure is adapted from Åkerström and Gram,
Free Rad
Biol Med
74 (2014) 274
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