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.