Iron is the most common chemical element found on earth, and it plays a key role in the biochemical processes of almost all organisms. Though iron is an important building block of life, it is also attributed to causing cellular damage when it is released into its free catalytic form. Researchers at the University of Alabama at Birmingham recently published a report in the Journal of Clinical Investigation which sought to help understand the relationship between the protein ferritin and kidney damage caused by this free iron. This study set a foundation for future research into potential treatments to prevent acute kidney injury.
(Image courtesy of UAB News)
Iron is commonly found in biological processes because it readily accepts and donates electrons to and from other molecules. However, this flexibility means that iron that is free in the body will react with other atoms and disrupt charge balances. This can ultimately create free radicals that can cause heavy damage to other structures in the body, such as DNA. In particular, these free radicals are known to aggravate kidney damage because there is a high concentration of iron in heme proteins that line the kidney tubules.
To minimize the detrimental effects of iron without interfering with its biochemical use, a number of mechanisms have evolved in the human body, one of which is the protein called ferritin. Ferritin is the major regulator of intracellular iron. It has the capacity to convert large quantities of free iron to a safe, soluble, and bioavailable form by altering its charge.
“Ferritin is a giant globe that sequesters 4,500 iron ions in safe form, thus preventing acute kidney injury,” said Abolfazl Zarjou, M.D., Ph.D., in an article published by UAB News. Zarjou is part of the American Board of Internal Medicine Research Pathway at the University of Alabama, Birmingham. “If this mechanism is confirmed, and if we can find ways to manipulate H-ferritin, this work would provide a platform for targeting iron sequestration as a new therapy against acute kidney damage.”
Zarjou and Subhashini Bolisetty, Ph.D., are the lead co-authors of a recently published study that confirms that ferritin is one of the lead proteins that mop up free iron. In this study, Zarjou, Bolisetty, and other researchers at the University of Alabama at Birmingham genetically engineered mice without ferritin. Because previous studies have shown that completely removing ferritin from mice is fatal, the researchers cut out the DNA coding for ferritin only in cells with markers present in kidney nephrons. This allowed them to study the relationship between ferritin and the kidney only. The researchers then applied the chemotherapy agent Cisplatin to both mice lacking ferritin and mice with normal amounts. Cisplatin is known to create free radicals that damage tumor cells, but it also splits heme proteins which release free iron into the body and cause kidney damage.
The researchers found that the mice without ferritin experienced a 40% worsening of kidney function after three days of Cisplatin treatment as compared to the mice with normal amounts of ferritin. This indicates that ferritin is an important player when it comes to regulating iron to prevent kidney damage. Zarjou and Bolisetty are hopeful that further research into ferritin will provide insight into potential therapies for preventing kidney damage.
(The University of Alabama, Birmingham campus, courtesy of the UAB website)
Funding for this study was provided by grants from the National Institutes of Health, the American Heart Association, and the UAB-UCSD O’Brien Center. For more information about research grants and funding statistics of the University of Alabama at Birmingham, click the link below for our UAB Funding Statistics report:
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