Cell boundaries are made up of lipids. When cells are severely damaged, these lipids need to be removed quickly to prevent toxicity and facilitate tissue healing. Researchers have found that a small, ancient protein, Seryl Amyloid A (SAA), plays a key role previously unknown in this vital process.
It has long been known that SAA redirects the transport of lipids during inflammation, but the biological significance of this deviation remains enigmatic. An important property of this protein is that your blood levels rise rapidly and dramatically (over a thousand times) during an acute infection, injury, inflammation or after surgery. How does this dramatic but transient increase help the body survive these acute events?
Now, Boston University School of Medicine (BUSM) research has found that SAA plays a number of previously unknown roles in transporting lipids needed to clean cell debris from injury sites. The studies were led by corresponding author Shobini Jayaraman, Ph.D., senior scientist in the department of Physiology and Biophysics.
"Our study provides insights into SAA's key beneficial function that helps us survive injury, infection, and inflammation." In other words, our study helps establish the raison d'être of this ancient enigmatic protein, "explained lead researcher Olga Gursky , Ph.D., professor of physiology and biophysics at BUSM.
The researchers used the recombinant SAA protein generated in the laboratory of Marcus Fändrich, professor and director of the Institute of Protein Biochemistry at the University of Ulm, Germany. The detailed biochemical analysis by Jayaraman found that SAA not only supplied lipid nanoparticles of proteins that are necessary for the breakdown of lipids, but also helped to remove their toxic insoluble products. Removal of such products is necessary to avoid their toxic effects. These in vitro studies suggest a dual role for ASA in the removal of lipid debris from dead cells in vivo.
According to the researchers, because SAA has been highly conserved for at least 500 million years, it must have been beneficial to survival. "Our study proposes such a beneficial role and binds SAA to another ancient acute phase protein, secretory phospholipase A2 (sPLA2)." Our results suggest that, together, SAA and sPLA2 act quickly and efficiently to remove lipids from injured sites. is necessary for tissue healing in vivo. We propose that this removal of lipids has helped several organisms to survive lesions and infections throughout evolution. "
Researchers hope that this and other related studies will ultimately help improve the treatment of acute inflammation and may lead to better understanding and ultimately alleviate chronic inflammation in which the deposition of SAAs in the kidneys and other organs is a serious complication.
These findings appear online in the journal eLife.
Study finds that acid-damaging protein triggers life-threatening illness
Shobini Jayaraman et al., Synergy between serum amyloid A and secretory phospholipase A2 suggest a vital role for an early protein in lipid elimination, eLife (2019) DOI: 10.7554 / eLife.46630
Researchers discover a new beneficial function of an ancient protein (2019, May 21)
recovered May 21, 2019
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