Home Reports Life Sciences Content

Gene that blocks free radical damage protects against emphysema

next article

02.11.2004

Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice

Emphysema is a major manifestation of chronic obstructive lung disease, which affects more than 16 million Americans and is the fourth highest cause of death in the United States. This disease is primarily cigarette smoke induced, but oxidative stress, a harmful condition that occurs when there is an excess of free radicals, has recently been alleged to play an important role in lung susceptibility to cigarette smoke-induced damage.

To investigate the impact of oxidative stress on emphysema development, Shyam Biswal and colleagues, from Johns Hopkins University, disrupted in mice the nuclear factor, erythroid-derived 2, like 2 (Nrf2) gene, which makes a protein that regulates genes involved in protecting the body from free radical damage. The authors found that cigarette smoke-induced emphysema was of earlier onset and more widespread in the Nrf2–/– mice than in their wild-type littermates. The Nrf2–/– mice also had a greater number of alveolar cells that underwent programmed cell death, and had more prominent bronchoalveolar inflammation.

Microarray analysis provided evidence of about 50 Nrf2-dependent antioxidant and cell-protective genes in the lung that might function together to protect the lung from cigarette smoke-induced emphysema. These data suggest that the Nrf2 pathway provides protection from emphysema by turning on antioxidants and suppressing inflammation and cell death in the lung.

Laurie Goodman | Source: EurekAlert!
Further information: www.the-jci.org

next article