•SQSTM1/p62 is ubiquitylated by TRIM21 at K7 via K63-linkage •p62 K7 ubiquitylation prevents its dimerization and sequestration •TRIM21 negatively regulates Keap1 sequestration and anti-oxidative response •TRIM21 null liver and heart are protected from oxidative tissue damage
Protein (p62), which is supposed to act as an antioxidant to prevent cell damage, was found not work efficiently in laboratory mice with liver and heart disease that mimicked these conditions in humans. This caused oxidative stress and allowed the release of harmful molecules, called free radicals, which resulted in serious illness. One of the body’s first lines of defense, the cells antioxidant response system is supposed to prevent these harmful invaders from causing a domino effect and damaging other cells.
Prof Wei-Xing-Zong said the damage occurred because another protein, (TRIM21) – which should activate the body’s response system to fight off bacteria and virus – did the opposite in these seriously ill mice and shut the antioxidant protein down, preventing it from doing its job. “The (TRIM21) protein exists naturally in our body; without it, we could easily succumb to other manageable infections,” said Zong. “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.”
Mice in which the TRIM21 gene was inactivated suffered little heart or liver damage when put through the same laboratory procedures used to produce tissue damage in mice with the gene. “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,” said Zong. “We believe this evidence is a truly important step to determining how to effectively treat these conditions in humans.”
Heart disease is the leading cause of death in the United States while 1 in 10 Americans has some form of liver disease. This study indicates how critical it is to carefully control oxidative stress – which can also lead to neurodegenerative diseases like Parkinson’s and Alzheimer’s, chronic fatigue syndrome, cancers and gene mutations as well as liver and heart disease – so that cell or tissue damage doesn’t occur. They believe that drugs could be developed that would reduce or stop the activity of the protein that is causing damage and preventing the antioxidant response from occurring.
http://news.rutgers.edu/research-news/heart-and-liver-disease-linked-antioxidant-shutdown/20160329.VvvTc3rQOTw
Recent Comments