Deoxydihydroceramide is Required for Much of the Cell Death Following Hypoxia

Researchers here provide evidence to show that a single type of ceramide, deoxydihydroceramide, is responsible for the tissue death following deprivation of oxygen, hypoxia, such as occurs after a heart attack. Suppressing levels of this ceramide rapidly enough in response to the event can reduce the damage. This is one of a number of lines of research focused on attempting to preserve cells following transient hypoxia by sabotaging the mechanisms that lead to cell death.

Heart attack and stroke are the primary cause of death worldwide. When a blood clot forms, it blocks the blood vessel and blood circulation. The non-irrigated tissues no longer receive oxygen and rapidly undergo necrosis, from which they cannot recover. But what causes the necrosis under these conditions? Not all animals are so sensitive to the absence of oxygen, worms can live three days without oxygen, some turtles can live several months, and certain bacteria indefinitely.

The researchers saw that in worms a particular species of ceramide, deoxydihydroceramide, accumulated to dangerous levels under anoxia, that is when tissues were completely deprived of oxygen. Upon an infarct, the synthesis of deoxydihydroceramide increases and becomes toxic for cells. Using mass spectrometry, researchers observed that this ceramide blocks certain protein complexes and provokes defects in the cytoskeleton of cells and the proper function of mitochondria, causing tissue necrosis.

Based on these results, researchers injected an inhibitor of ceramide synthesis in mice just before a heart infarct. They found that the mice that received the injection have 30% less tissue necrosis when compared to control mice that received an injection without the inhibitor. The researchers are now working on an inhibitor that will target more specifically deoxydihydroceramide, which is likely to have fewer side effects and maintain the normal body functions of ceramides.



Mmm... I wonder whether this could be useful for cryonics.

Posted by: Antonio at October 25th, 2019 7:06 AM

Interesting indeed. I all not sure about the cryonics but it for sure can be used for extreme sports like deep diving, for example. I would expect species exposed to apoxya to have mutations reducing the synthesis of ceramide. Species like dolphins, seals, naked mole rats, and why not human populations living from diving across many generations. Or, possibly Sherpas and native Peruvians

Posted by: Cuberat at October 25th, 2019 7:49 AM

Useful for just general survival. Accidents will always happen, and you'll have much better odds of surviving them if you have brain cells which can go without oxygen for four hours rather than the current five minutes. Our cells are ridiculously fragile, and that's something that needs to be addressed just as much as aging.

Posted by: Arcanyn at October 25th, 2019 11:22 AM

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