Peroxiredoxin's Role in Erythrocyte Antioxidant Defense and Tumor Suppression

Carola A. Neumann, MD
Harvard Medical School
T32ES07155

Background: Hydrogen peroxide, known mostly as a common antiseptic, is also a product of aerobic metabolism. As an organism consumes oxygen, small amounts of hydrogen peroxide and other similar reactive oxygen compounds are formed as by-products. All aerobic organisms have evolved systems to control the concentrations of reactive oxygen compounds so that they don't accumulate in quantities sufficient to kill or damage cells. One such mechanism is the enzyme peroxiredoxin. Peroxiredoxin and other enzymes, such as catalase, act to destroy reactive oxygen compounds. The story might end there, but there is a growing body of evidence that reactive oxygen compounds are important for cell signaling and communication and have also been implicated in cancer development and aging.

Advance: This publication by an NIEHS-supported post-doctoral fellow demonstrates that transgenic mice with targeted inactivation of the peroxiredoxin gene, Prdx1, are viable and fertile but have a shortened life-span from development of severe hemolytic anemia and several cancers beginning at about nine months of age. These effects are also seen in heterozygotes. The anemia is characterized by an increase in red blood cell in reactive oxygen species, which lead to protein oxidation, hemoglobin instability, and decreased red blood cell life. The cancers include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this enzyme functions as a tumor suppressor.

Implication: These results indicate that Prdx1 as an important defense against the actions of reactive oxygen compounds in red blood cells and tumor progression in aging mice and presumably in humans as well. Establishing the mechanisms underlying the cancer susceptibility of Prdx1 mutant mice will require further studies. These mice should provide a valuable tool for understanding the role of antioxidant pathways in aging, carcinogenesis, and other processes.

Citation: Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, and Van Etten RA. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defense and tumor suppression. Nature. 2003 July 31;424:561-5.