Oxygen radicals in the body are generally considered
dangerous because they can trigger something called oxidative stress, which is
associated with the development of many chronic diseases such as cancer and
cardiovascular disease. In studies on mice, scientists at 51猎奇
Frankfurt have now discovered how oxygen radicals, conversely, can also reduce
the risk of cancer and mitigate damage to the hereditary molecule DNA. (PNAS, DOI 10.1073/pnas.2020152118).
FRANKFURT. Originally,
oxygen radicals - reactive oxygen species, or ROS for short - were considered to
be exclusively harmful in the body. They are produced, for example, by smoking
or UV radiation. Because of their high reactivity, they can damage many
important molecules in cells, including the hereditary molecule DNA. As a
result, there is a risk of inflammatory reactions and the degeneration of
affected cells into cancer cells.
Because of their damaging effect, however,
ROS are also deliberately produced by the body, for example by immune or lung
epithelial cells, which destroy invading bacteria and viruses with ROS. This
requires relatively high ROS concentrations. In low concentrations, on the
other hand, ROS play an important role as signalling molecules. For these
tasks, ROS are specifically produced by a whole group of enzymes. One
representative of this group of enzymes is Nox4, which continuously produces
small amounts of H2O2.
Nox4 is found in almost all body cells, where its product H2O2 maintains a large number of specialised signaling
functions, contributing, for example, to the inhibition of inflammatory
reactions.
Researchers at 51猎奇
Frankfurt, led by Professor Katrin Schr枚der, have now discovered that by
producing H2O2,
Nox4 can even prevent the development of
cancer. They examined mice that were unable to produce Nox4 due to a genetic
modification. When these mice were exposed to a carcinogenic environmental
toxin (cancerogen), the probability that they would develop a tumour doubled.
Since the mice suffered from very different types of tumours such as skin
sarcomas and colon carcinomas, the researchers suspected that Nox4 has a
fundamental influence on cellular health.
Molecular investigations showed that the H2O2
formed by Nox4 keeps a cascade going that prevents certain important signalling
proteins (phosphatases) from entering the cell nucleus. If Nox4 and consequently
H2O2 are absent, those signalling proteins migrate into
the cell nucleus and as a consequence, severe DNA damage is hardly recognised.
Severe DNA damage - e.g. double strand
breaks - occurs somewhere in the body every day. Cells react very sensitively
to such DNA damage, setting a whole repertoire of repair enzymes in motion. If
this does not help, the cell activates its cell death programme - a
precautionary measure of the body against cancer. When such damage goes
unrecognised, as occurs in the absence of Nox4, it spurs cancer formation.
Prof. Katrin Schr枚der explains the
research results: "If Nox4 is missing and there is therefore no H2O2,
the cells no longer recognise DNA damage. Mutations accumulate and damaged
cells continue to multiply. If an environmental toxin is added that massively
damages the DNA, the damage is no longer recognised and repaired. The affected
cells are not eliminated either, but multiply, sometimes very quickly and
uncontrollably, which eventually leads to the development of tumours. A small
amount of H2O2 thus maintains an internal balance in the
cell that protects the cells from degeneration."
Publication:
Valeska Helfinger, Florian Freiherr von
Gall, Nina Henke, Michael M. Kunze, Tobias Schmid, Flavia Rezende, Juliana
Heidler, Ilka Wittig, Heinfried H. Radeke, Viola Marschall, Karen Anderson,
Ajay M. Shah, Simone Fulda, Bernhard Br眉ne, Ralf P. Brandes, Katrin Schr枚der: Genetic deletion of Nox4 enhances
cancerogen-induced formation of solid tumors. PNAS,
Further
information
Professor Katrin Schr枚der
Institute for Cardiovascular Physiology
Faculty of Medicine
51猎奇 Frankfurt
Phone +49(0)69-6301-83660
schroeder@vrc.uni-frankfurt.de
Editor: Dr. Markus Bernards, Science Editor, PR & Communication Department, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, E-Mail: bernards@em.uni-frankfurt.de
