In the December 1 issue of the Journal of Clinical Investigation, Teresa Tessner and colleagues from the Washington University School of Medicine pursued the mechanism by which PGE2 protects against radiation-induced injury in mice. They demonstrate that radiation-induced cell death can be dependent or independent of the bax protein, however the beneficial effect of PGE2 treatment is only achieved via a bax-dependent mechanism. Bax is normally expressed in the cell cytoplasm, however in response to radiation exposure, bax relocates to the mitochondrial membrane and trigger cell signaling events that lead to cell death. Administration of PGE2 to radiation-exposed mice was found to activate AKT phosphorylation events that block the relocation of bax within the cell, and therefore prevent cell death.
The data suggest that PGE2 or other drugs that increase AKP phosphorylation should reduce injury to the small intestine during radiation therapy. Conversely, cancers with mutations that inactivate bax and block its relocation to the mitochondria may be resistant to radiation therapy. This work may have significant clinical impact if the use of PGE2 could be shown to be effective for protection against radiation-induced gut injury in humans.
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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-0497
Journal of Clinical Investigation
1-Dec-2004