PITTSBURGH -- A University of Pittsburgh study fully describes for the first time an important but complicated cell-death pathway that can destroy healthy cells, resulting in tissue and organ damage.
The pathway is responsible for a serious asthma attack, excess traumatic brain damage and kidney failure, among other health problems.
Published online Thursday in the journal Cell, the Pitt study identifies a key protein in the cell-death pathway known as ferroptosis, typically a healthy and necessary process that uses iron to kill already damaged or malfunctioning cells then recycles them safely and efficiently.
That protein -- PEBP1 -- serves as the pathway warden in controlling whether a certain enzyme, 15LO, ends up making a fat molecule or lipid, OOH-Pes, in such volumes that they signal the activation of the cell-death process.
With the study now describing the entire process, Pitt researchers already are working to design drugs to prevent the warden protein and enzyme from combining, with the goal of halting cell destruction.
"Better treatments for traumatic brain injury and acute kidney injuries are desperately needed," stated Hulya Bayir, research director of Pediatric Critical Care Medicine at Children's Hospital of Pittsburgh of UPMC, and a researcher in the study.
The study's senior author Valerian Kagan, a professor in Pitt's Graduate School of Public Health's Department of Environmental and Occupational Health, was key in discovering the protein's important role in the cell-death process.
Sally Wenzel, a professor of medicine in Pitt's School of Medicine and director of the University of Pittsburgh Asthma Institute at UPMC, led the study with her focus on the possible pathway leading to asthma exacerbation.
For some people with asthma, she said, a virus, air pollution or even cigarette smoke can trigger oxidative stress, which among other effects, could inhibit a good protein necessary to control cellular mucus production. With that protein suppressed, dangerous lipids likely would be generated that signal the cell-death process. One potential result is the destruction of mucus-producing airway cells, that could cause them to release their entire supply of mucus into the airways. Resulting airway restrictions can require emergency treatment, she said.
"Asthma is not just about stopping an attack, it's also about preventing them -- and both are a major unmet need among patients," Dr. Wenzel said in a statement. "Our study identifies how ferroptotic death signals can damage the cells lining the airway. Targeting these pathways could lead to preventative and treatment options for asthma exacerbations."