News Release 23-Apr-2021
Editor’s note: Does this study mean that all oxygen radicals generated by different means are equally protective? The answer is no! First all, yes, our body constantly generates some oxygen radicals to maintain our health or physiologic needs. But the generation of these oxygen radicals is well regulated and tightly controlled. Exogenous oxygen radicals brought in our body through foods or pollutants or generated due to exposure to ionizing radiations are not welcome and our body feels the stress and have to try to neutralize them, which in most cases is not as effective because our defense capacity is no match for the potential damage imposed on us. As a result, these exogenous or oxygen radicals induced by radiation can damage all sorts of our issues/cells/molecules leading to premature aging, chronic diseases like cancer.
編者註：這項研究是否意味著通過不同方式產生的所有氧自由基都具有同等保護性？ 答案是不！ 首先，是的，我們的身體不斷產生一些氧自由基，以維持我們的健康或生理需求。 但是這些氧自由基的產生受到良好調節和嚴格控制。 通過食物或污染物帶入我們體內或由於暴露於電離輻射而產生的外源氧自由基是不受歡迎的，而且我們的身體會感到壓力並必須設法中和它們，在大多數情況下這種效果不那麼有效，因為我們的防禦能力沒有 匹配對我們施加的潛在損害。 結果，由輻射誘發的這些外源或氧自由基會破壞我們的各種問題/細胞/分子，從而導致早衰，慢性疾病（例如癌症）。
Goethe University researchers investigate oxidative stress in mice
Goethe University Frankfurt
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 Goethe University Frankfurt, led by Professor Katrin Schröder, 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 Schröder 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.”