Selenium is a constituent of at least 25 essential proteins (selenoproteins), including several antioxidants that protect cells against oxidative stress and disease. A team of researchers from Munich in Germany has mapped out the mechanisms, which the selenium-containing antioxidants use to protect neurons in the brain against cell death. The scientists see a whole new potential with selenium because of its ability to protect against neurological disorders and cancer. It is problematic, however, that we have widespread selenium deficiency in our part of the world. Even if you stick with the official dietary guidelines, it is very difficult to get enough selenium to saturate all the different selenoproteins.
Selenium was discovered over 200 years ago by the Swedish scientist Jacob Berzelius. The chemical element was named after Selene, the Greek goddess of the moon. Selenium is used in the chemical industry among other places. Selenium and selenium salts are toxic in large quantities, and science has only known for a few decades that a number of organic selenium compounds are essential. They play an important role in our energy turnover, metabolism, immune defense, fertility, and not least as support for several different antioxidants that protect cells against oxidative stress.
The body is exposed to oxidative stress when the balance between antioxidants and free radicals is disturbed. Free radicals are aggressive molecules that initiate dangerous chain reactions inside and between the cells. Free radicals are a byproduct of our respiration, and the number of free radicals increases tremendously in response to stress, ageing processes, inflammation, poisoning, smoking, and radiation. In fact, free radicals and oxidative stress are involved in the majority of diseases and in cell death.
Uncovering an old mystery
A team of scientists from the Institute Developmental Genetics (IDG) in Helmholtz Zentrum München has now uncovered an old mystery, which helps explain why the selenium-containing antioxidants are so essential.
Under normal circumstances, worn-out or diseased cells are supposed to execute programmed cell death or apoptosis, thereby freeing space for new cells. Needless to say, the cells must be protected as much as possible against oxidative stress, wear and tear, and disease, and their self-destruction should never get out of hand.
For years, the researchers have studied the process of a recently discovered type of programmed cell death called ferroptosis that involves iron (ferro = iron). It turns out that the selenium-containing enzyme GPX4 (glutathionine peroxidase 4), in itself a powerful antioxidant, plays a major role.
In order to get a better understanding of the process, the researchers studies mice whose GPX4 had been manipulated by replacing the content of selenium with sulfur, with which selenium bears certain resemblances. However, sulfur is not an antioxidant.
They found that the mice whose selenium in GPX4 had been replaced with sulfur were unable to survive for more than three weeks, and the mice died of neurological complications.
When selenium-containing GPX4 antioxidants are lacking, special neurons are lost
The scientists then identified some special neurons that were absent in the brains of the mice that lacked the selenium-containing GPX4 antioxidants. Later studies showed that these neurons were lost in the brains as they developed after birth in those mice where selenium had been replaced with sulfur in the GPX4 antioxidants.
The researchers were also able to show that ferroptosis is triggered by oxidative stress, which can also result from high metabolic activity and high activity in the neurons.
For the first time ever it is shown that selenium plays an essential role in the development and maintenance of a special type of neurons after birth. The selenium-containing GPX4 antioxidants simply protect these neurons against oxidative stress and cell death caused by ferroptosis.
In future studies, Marcus Conrad and his team of researchers from Munich plan to look closer at how ferroptosis is initiated in the cells and under which conditions. The aim of such studies is to prevent or ameliorate cancer and neurodegenerative diseases, which are currently difficult to treat. It appears that selenium plays a determining role, provided we get enough to saturate GPX4 and the other selenoproteins.
Facts on selenium, GPX, and cell death
It is difficult to get enough selenium, even if you eat a healthy diet
Selenium is mainly found in fish, shellfish, organ meat, eggs, dairy products and Brazil nuts (the richest source), but European crops are generally low in selenium. Even though seafood is generally considered a rich source of selenium, you cannot get enough of the nutrient by consuming fish and shellfish five days a week, according to a Danish study.
100 micrograms of selenium daily is able to saturate an important selenoprotein
Selenoprotein P is an important selenium-containing protein and is used as a marker of blood selenium status. Studies show that the RI (reference intake) of 50-70 micrograms per day is not sufficient to saturate selenoprotein P. This requires at least 100 micrograms of selenium daily.
HELMHOLTZ ZENTRUM MÜNCHEN – GERMAN RESEARCH FOR ENVIROMENTAL HEALTH
Lutz Shomburg. Dietary Selenium and Human Health. Nutrients 2017
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