Failing Antioxidant Mechanisms Linked To Heart And Liver Disease

Credit: K Sandberg

Failure of a protein involved in the cell's antioxidant response could play a role in heart and liver disease

Scientists have discovered that a protein called p62 stops working effectively in mice with liver and heart disease. p62 is involved with sensing and clearing toxic cellular material. It also helps to mount a protective, antioxidant response by freeing another activating protein called Nrf2 which kick-starts the cell's antioxidant mechanisms in response to stress. When something goes wrong with this pathway, cells are exposed to higher levels of oxidative stress and lessened recyling. 

Shutting down a faulty process

Another protein called TRIM21 is usually responsible for an anti-pathogen response - helping to degrade any foreign invaders that enter the cell. While this is normally a good thing, researchers found in mice with heart and liver disease TRIM21 isn't working properly; it was shutting down antioxidant mechanisms through acting on p62 instead. 

"The (TRIM21) protein exists naturally in our body; without it, we could easily succumb to other manageable infections. But this study has shown us that when we run into severe pathological conditions like heart and liver disease it would be more beneficial to inhibit the TRIM21 protein because it is preventing the cell from protecting itself against damage"

Interestingly when mice with an inactivated TRIM21 gene were exposed to tissue damage that would normally lead to heart damage, they didn't seem to be affected. For some reason, TRIM21 becomes harmful in these specific organs when it comes to damage - increasing disease likelihood and dampening down protective mechanisms. 

"The hearts and livers of the mice without the TRIM21 gene seemed to be well protected which was opposite of the mice with the gene. We believe this evidence is a truly important step to determining how to effectively treat these conditions in humans"

The research also highlights how important balance is in cellular health; too much or too little of anything can mess everything up. While TRIM21 can be harmful in certain circumstances, there is evidence that cutting activity can increase cancer risk too. Achieving the right balance of stress and protection is really important in maintaining overall organism health, and learning exactly what makes things go pear shaped and when, opens up new potential treatments to avoid disease. 

Read more at MedicalXpress