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Protein thought to protect against oxidative stress also promotes clogging of arteries
Date:1/10/2011

ere specially bred without the protein.

Researchers found that male mice without Nrf2 had decreased levels of antioxidants, as would be expected, but also exhibited a 53 percent reduction in atherosclerotic plaques in the aorta, compared with normal animals. Mice with only half the gene expression for Nrf2 exhibited the same degree of plaque formation as normal animals.

The team then tried to arrive at a better understanding of what was going on by evaluating several factors that could be affected by the Nrf2 protein.

Scientists found that the mice without any Nrf2 had lower levels of total cholesterol in the blood and lower amounts of cholesterol in the liver. The protein deficiency also led to reduced expression of the genes involved in synthesizing and storing fat and regulating glucose in the liver, which are part of the process of manufacturing cholesterol.

According to Araujo, the study findings point to new and important effects of the Nrf2 protein in regulating cholesterol production as well as antioxidant pathways.

"The cholesterol effects may need to be taken into consideration when developing antioxidant therapies using this protein," said Fen Yin, a co-author of the study and a research associate in the division of cardiology at UCLA. "The dosage or level of this gene expression could be important to balance the two effects."

In addition, investigators found that most of the effects of Nrf2 were more highly prevalent in the male mice. More studies will be needed to examine whether these sex differences in the animal model would be similar in humans.

Araujo noted that more research will also assess whether other environmental, metabolic and genetic elements play a role in the impact of Nrf2 on cholesterol and antioxidants.


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Contact: Rachel Champeau
rchampeau@mednet.ucla.edu
310-794-2270
University of California - Los Angeles
Source:Eurekalert

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