Pan European Networks - Horizon 2020 - page 180

N
ew results from Lund University have shown that a small
human protein called alpha-1-microglobulin (A1M) is a
vital part of the housekeeping machinery in humans
and all vertebrate organisms. It does a job which is basic, boring,
taken for granted and often neglected: cleaning of cells, tissues
and extracellular spaces. This has led to proposals for new
principles of treatment of diseases where accumulation of waste
products is a major pathological factor, and therefore increased
cleaning capacity by infusion of A1M may be an efficient
treatment principle. Treatments for several such diseases are now
being developed and, of these, pre-eclampsia and atherosclerosis
are particularly interesting.
Oxidative stress – accumulation of chemical
waste products
Why do we need to clean the tissues of our body? The answer to
this is, of course, complicated, but it may be addressed by a slight
over-simplification: because the chemical reactions that make our
bodies work constantly produce unwanted, toxic side products, or
waste products. The waste products need to be eliminated quickly
before they react with healthy cellular and extracellular molecules
and cause damage to them. The billions upon billions of chemical
reactions that constitute the process we call ‘life’ must be strictly
controlled spatially and temporally in order to maintain life and
prevent chaos.
To minimise the production of unwanted chemical substances –
waste products – our bodies are compartmentalised into organs,
tissues, cells and subcellular organelles. When this partitioning
is disrupted during disease, wounding, infection or inflammation
etc., the production of waste products is increased. Many of
these waste products are of a certain kind – free radicals. The
free radicals are usually oxidative, which means that they ‘steal’
electrons from healthy cellular and tissue molecules. Over-
production of the waste products is therefore called ‘oxidative
stress’. Respiratory metabolism, oxygen transport and ultraviolet
(UV) irradiation are three major examples of physiological
processes that are notorious in producing waste products in the
form of free radicals.
Respiratory metabolism
The respiratory metabolism takes place in small organelles –
mitochondria – which are found in their thousands in each cell.
Here we burn food (mostly carbohydrates and fats) to produce
the energy needed to operate our bodies. The energy is stored in
units called ATP, which can be transported and utilised wherever
and whenever energy is needed. Mitochondria are the power
plants of our body. Like most power plants leak heat, smoke and
waste products, the mitochondria produce small amounts of
free radicals. Mitochondria are hidden deep in the cells, and
normal free radical production is not usually a big problem in
health, but when cells are broken, for instance during
inflammation or wounding, the leakage of free radicals
contributes to the disease development.
Oxygen transport
Mitochondria need oxygen to burn fat and carbohydrates and to
produce energy. Oxygen has a natural tendency to react with other
biological molecules in a chemical process called ‘oxidation’. This
is what we see in a rusting car or a rotting apple. In fact, the
mitochondrial power plants have tamed the almost explosive
reactivity of oxygen, turning it into the usable energy packages
called ATP. Mitochondrial respiration is a very important and
fundamental component of the life process. However, in
multicellular higher organisms such as humans, the transporting
of oxygen from air to mitochondria is a huge infrastructural task.
There are two main problems: first, the challenge of the transport
from the alveoli of the lungs to each of the approximately one
quintillion mitochondria in a human body is enormous; second,
how can we keep oxygen from reacting with all the other
molecules encountered on the way? Both problems are taken
care of by our red blood cells and their cargo – haemoglobin.We
have a little more than half a kilogram of haemoglobin packed in
the red blood cells and its job is to carry all the oxygen we need
all the way from the lungs to the mitochondria in every corner of
our body. Keeping the oxygen bound to the haemoglobin
molecules prevents it from reacting with the blood vessel walls
and other molecules on its way in an uncontrolled oxidising
reaction. The danger of the transported oxygen becomes apparent
in haemolytic diseases – when the red blood cells break and
haemoglobin-oxygen leaks out. Such diseases, for example sickle
cell disease, and transfusion reactions lead to high blood
pressure and acute kidney damages, the latter because kidneys
are the most intensely blood-perfused organs.
UV irradiation
We are exposed to high doses of ionising irradiation every day. UV
irradiation from the Sun, mostly, as well as other forms, e.g. so-
called ‘cosmic irradiation’, reaches the surface of our bodies and
penetrates predominantly the skin, hair and eyes to some depth.
The irradiation consists of small packages of energy that can
introduce chemical changes into healthy molecules, producing
Could our own bodily process of cleaning body tissue be the start of a new road
towards disease treatment and sustainable health?
A new, cleaner road
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I S S U E S I X
H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
P R O F I L E
H E A L T H : D I S E A S E R E S E A R C H
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