Many heart attacks occur in the early hours of the morning. But not only heart problems: many other diseases usually appear first thing in the morning. Now, an investigation of Weizmann Institute of Science (Israel), has discovered a possible explanation for this mysterious phenomenon.
In a study published in ‘Cell Metabolism‘, scientists discovered that a key component of our circadian clock (the internal 24-hour molecular clock that operates in every cell) also regulates the body’s response to oxygen deficiency. This component, which undergoes changes throughout the day and night, could affect the timing of disease outbreaks that are influenced by the body’s oxygen cycle.
As breathing beings, our ability to detect and respond to a lack of oxygen is as vital to us as the air we breathe.
He 2019 Nobel Prize in Physiology or Medicine was awarded to three researchers who discovered hypoxia-inducible factor 1-alpha (HIF-1α), the key protein that determines how each cell responds to a lack of oxygen.
As long as there is enough oxygen, the protein remains unstable and breaks down quickly; but when there is a shortage of oxygen, it stabilizes, accumulates and enters the nucleus of cells where it activates numerous vital genes to respond to oxygen deficiency.
However, it turns out that HIF-1α is not the only key factor.
The study found that the BMAL1 protein, a key component of our circadian clocks, also plays an important role in the body’s response to oxygen deficiency and is required to stabilize and activate the HIF-1α protein.
Furthermore, it suggests that BMAL1 is more than just a “booster” and that it plays a role independent of HIF-1α in activating the body’s plan to cope with oxygen deprivation. These new findings could explain why the body’s response to oxygen deficiency and its coping with various medical conditions change throughout the day and night.
Protein by day, protein by night
The work showed that the HIF-1α and BMAL1 proteins are key to activating the genetic mechanisms necessary against hypoxia. Using genetically modified mice that lacked one or both proteins in the liver, the researchers found that HIF-1α did not accumulate without BMAL1, affecting the response to hypoxia. Furthermore, mice without both proteins presented high mortality under hypoxia during the nightassociated with circadian variations of BMAL1.
Surprisingly, although the mice had mild liver damage, the cause of death was linked to low lung capacity to absorb oxygen, a phenomenon similar to hepatopulmonary syndrome in humans. This animal model could help investigate mechanisms of this condition and develop new therapies.
«We have identified an increase in the production of nitric oxide in the lungs, which causes dilation of blood vessels. As a result, blood flows through the lungs much more quickly and does not deliver oxygen efficiently,” the authors write.
However, they acknowledge that they still do not know by what mechanisms liver damage affects lung function, but the initial findings from our genetic mouse model point to an interesting group of proteins that could be part of the communication between the liver and the lungs. .
«In mice that developed hepatopulmonary syndrome, this communication was altered. If you are proteins are also produced in humans and are really related to the syndrome, they could serve as a target for future therapy,” they conclude.
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