AsianScientist (May 29, 2014) – Normally associated with the inflammatory disease gout, uric acid has now been shown to function as an important intracellular antioxidant in a pathway controlled by the tumor suppressor p53. This research has been published in the journal Oncogene.
Traditionally, uric acid has a bad reputation because high levels of the compound are associated with gout and other medical conditions. However, uric acid has also been proposed to act as an antioxidant that prevents aging. Since only humans and higher primates maintain high blood levels of uric acid near saturated levels, uric acid has been speculated to be one reason humans live so much longer than animals such as dogs and cats.
The present study, led by assistant professor Koji Itahana of Duke-NUS Graduate Medical School Singapore (Duke-NUS), showed how cells used uric acid as an antioxidant to prevent the accumulation of reactive oxygen species (ROS). ROS are molecules containing highly reactive oxygen that cause cell damage known as oxidative stress which has been proven to cause aging, cancer, cardiovascular and neurodegenerative diseases.
Itahana and his team showed that the transporter protein SLC2A9 was responsible for the uptake of uric acid from the environment and that SLC2A9 was upregulated in a p53-dependent mechanism. This is significant as p53 is a key tumor suppressor that is mutated in about half of all cancers worldwide.
Understanding this novel antioxidant pathway could enable researchers and clinicians to better understand how to prevent aging and other such diseases. Interestingly, Itahana also showed that shutting down the SLC2A9 antioxidant pathway in cancer may be an unorthodox way to target cancer once the patient already has the disease.
“While the p53-SLC2A9 mechanism is a way of preventing disease in a healthy body, once the body already has cancer, disrupting that same mechanism may be a way to kill the cancer since cancer has already very high levels of ROS.”
“For instance if a patient were to take probenecid, a gout drug that inhibits the function of GLUT9 and a chemo drug, ROS levels would become so high that cancer cells may not be able to survive in the body because there is simply no space,” explained Itahana.
The article can be found at: Itahana et al. (2014) The Uric Acid Transporter SLC2A9 is a Direct Target Gene of the Tumor Suppressor p53 Contributing to Antioxidant Defense.
—–
Source: Duke-NUS Graduate Medical School; Photo: lunar caustic/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
