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By impounding iron, FHC foils cell suicide, fuels inflammation

A research team based at the University of Chicago may have found a way to manipulate cell suicide, also known as programmed cell death, a normal process that regulates cell number but that goes awry in chronic inflammatory disorders, cancer and other diseases.

In the 12 Nov. 2004 issue of the journal Cell, the scientists show that a key step in the process of preventing cell suicide is the induction of ferritin heavy chain (FHC), a protein that collects and hoards iron. By sequestering iron -- which cells with suicidal tendencies need to make the harmful substances that induce death -- FHC prevents cellular suicide.

This finding suggests that drugs that modulate FHC or iron metabolism could provide a new and effective approach to anti-inflammatory therapy without the side effects, such as weakening the immune system, that come with current treatments.

"In a long and complicated biochemical chain, this is one of the final links, which is exactly what we want," said study author Guido Franzoso, M.D., Ph.D., associate professor in the Ben May Institute for Cancer Research at the University of Chicago. "If we tamper with the front end, it changes everything, but boosting or blocking a downstream component allows us to select for a specific response."

Programmed cell death, also known as apoptosis, is the mechanism all multi-cellular organisms use to eliminate excess or damaged cells. Each year, through a balance of cell death and cell division, humans lose and regain a mass of cells roughly equal to their weight.

When a virus attacks an organism, for example, infected cells commit suicide to protect their healthy neighbors. At the same time, white blood cells multiply rapidly to battle the invader. Once the virus is eliminated, however, most of those virus-chasing white blood cells orchestrate their own demise. If they fail to thin their ranks sufficiently, they keep accumulating, infection after infection, which ca
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Contact: John Easton
John.Easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
11-Nov-2004


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