2014-05-07 / Health

New role discovered for enzyme could have implications for cancer and neurologic disease

Rutgers Cancer Institute of New Jersey research published in ‘Nature Communications’

Research from Rutgers Cancer Institute of New Jersey shows that a new function discovered for a longstudied enzyme could have implications for the diagnosis and treatment of some cancers and neurological disease.

The work involves superoxide dismutase 1 (Sod1), an enzyme that for nearly half a century has been known to remove a specific radical byproduct created during the energy-producing process of cell metabolism.This ‘superoxide’byproduct comes from a family of byproducts known as reactive oxygen species (ROS). These byproducts can modify fats, proteins and DNA in a chemical reaction called oxidation, causing these biological molecules to lose functions. Low levels of these byproducts can cause normal cells to become cancerous.At higher levels, cell death and damage to tissues and organs can occur.

In the study, published in the current edition of Nature Communications (doi: 10.1038/ncomms4446), X.F. Steven Zheng, Ph.D., and colleagues show that when cells have a high content of ROS byproducts and are under oxidative stress, the Sod1 enzyme helps to remove other types of ROS byproducts in addition to superoxides by controlling the production of many different types of antioxidants in a process called transcription. Investigators found that this action is enabled through the Sod1’s communication with a protein known as ATM (ataxia telangiectasia mutated) that acts as a tumor suppressor and a neurological disease protein. ATM senses elevated ROS byproduct levels in the cell and activates the transcriptional function of Sod1.

Dr. Zheng, who is the senior author of the work and co-director of the Cancer Pharmacology and Preclinical Therapeutics Program at the Cancer Institute of New Jersey, notes the latter finding explains why ATM and Sod1 share common traits in some cancers and neurological disorders. For instance, Sod1 plays a key role in the development of liver and lung cancer. It also accounts for 20 percent of inherited cases of amyotrophic lateral sclerosis (ALS) — or Lou Gehrig’s disease. Sod1 also is associated with a vision-loss disorder known as age-related macular degeneration and diabetic complications.

“In identifying this new role for Sod1 in helping to control oxidative stress response, we can better understand the relationship between Sod1 andATM and their collective impact on ROS byproducts,” notes Zheng, who also is a university professor at Rutgers RobertWood Johnson Medical School. “Further research in this area could have considerable implications in the diagnosis and treatment of Sod1-related diseases such asALS and cancer.”

Along with Zheng, the author team consists of Chi KwanTsang, Cancer Institute and Robert Wood Johnson Medical School;Yuan Liu, Cancer Institute and Graduate Program in Molecular and Cellular Pharmacology at Rutgers University; JaniceThomas, Cancer Institute and Robert Wood Johnson Medical School; and Yanje Zhang, Cancer Institute and Robert Wood Johnson Medical School.

The study was supported by grants from the National Cancer Institute (R01- CA123391, R01-CA166575 and R01- CA173519).

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