Scientists identify major source of cells' defense against oxidative stressApril 09, 2012
Both radiation and many forms of chemotherapy try to kill tumors by causing oxidative stress in cancer cells. New research from USC on a protein that protects cancer and other cells from these stresses could one day help doctors to break down cancer cells' defenses, making them more susceptible to treatment.
In the March 23 issue of the Journal of Biological Chemistry, scientists led by USC Professor Kelvin J. A. Davies demonstrated that a protein known as Nrf2 governs a cell's ability to cope with oxidative stress by increasing the expression of key genes for removing damaged proteins.
Typically, oxidative stress is to be avoided. People eat foods high in antioxidants (such as fruits and vegetables) to try to block oxidation in their cells, in hopes of lowering their risk of illnesses such as cancer, heart disease, stroke and Alzheimer disease - which are all linked to oxidative stress.
But in the case of cancer cells, if the Nrf2 response could some day be selectively turned off, treatments like chemotherapy and radiation could be more effective, Davies said.
"One of the problems you have is that cancer cells start becoming resistant to those treatments: they adapt," said Davies, who holds joint appointments in the USC Davis School of Gerontology the USC Dornsife College of Letters, Arts and Sciences. "The next time they may be more resistant because they've seen it before."
Nrf2 is a transcription factor protein, meaning that it binds to specific sequences of DNA, turning on the process of copying the blueprints encoded in those DNA sequences into functional enzymes. In particular, the new work from the Davies lab shows that production of proteasome and a proteasome regulator (Pa28) is controlled by Nrf2 during oxidative stress. Proteosome, in turn, is a large protein enzyme that breaks down oxidized proteins that would otherwise accumulate and cause cells to die.
When oxidative stress increases (simulated in the lab by adding hydrogen peroxide - the major product of both radiation therapy and chemotherapy), Davies and his team found that the Nrf2 in a cell starts ramping up proteasome production.
The researchers then tested their findings by blocking Nrf2 with various chemical and genetic inhibitors, which in turn decreased the cell's ability to make more proteasome and cope with the hydrogen peroxide.
In normal young cells, Nrf2 allows continuous regulation of proteasome production in response to changing oxidative environments. This ability may decline in aging and age-related diseases, making older individuals less able to cope with stress.
"We would like to be able to reverse this decline in normal cells, while making cancer cells less stress-resistant and more easily killed by radiation therapy and chemotherapy," Davies said.
University of Southern California
Related Oxidative Stress Current Events and Oxidative Stress News Articles
Aspirin shown to benefit schizophrenia treatment
A new study shows that some anti-inflammatory medicines, such as aspirin, estrogen, and Fluimucil, can improve the efficacy of existing schizophrenia treatments. This work is being presented at the European College of Neuropsychopharmacology conference in Berlin.
Fish oil supplements have little effect on irregular heartbeat
High doses of fish oil supplements, rich in omega-3 fatty acids, do not reduce atrial fibrillation, a common type of irregular heartbeat in which the heart can beat as fast as 150 beats a minute.
Chemical derived from broccoli sprouts shows promise in treating autism
Results of a small clinical trial suggest that a chemical derived from broccoli sprouts - and best known for claims that it can help prevent certain cancers - may ease classic behavioral symptoms in those with autism spectrum disorders (ASDs).
Researchers identify 'Achilles heel' in metabolic pathway that could lead to new cancer treatment
Researchers at UT Southwestern Medical Center have found an "Achilles heel" in a metabolic pathway crucial to stopping the growth of lung cancer cells.
Vesicles influence the function of nerve cells
Tiny vesicles containing protective substances which they transmit to nerve cells apparently play an important role in the functioning of neurons.
Ancient protein-making enzyme moonlights as DNA protector
Scientists at The Scripps Research Institute (TSRI) have found that an enzyme best known for its fundamental role in building proteins has a second major function: to protect DNA during times of cellular stress.
Montmorency tart cherry juice lowered blood uric acid levels and a marker for inflammation
Tart cherries have long been researched for their association with pain relief - ranging from gout and arthritis joint pain to exercise-related muscle pain.
Blood test may help determine who is at risk for psychosis
A study led by University of North Carolina at Chapel Hill researchers represents an important step forward in the accurate diagnosis of people who are experiencing the earliest stages of psychosis.
Phthalates heighten risk for childhood asthma
Researchers at the Columbia Center for Children's Environmental Health at the Mailman School of Public Health are the first to demonstrate an association between childhood asthma and prenatal exposure to two phthalates used in a diverse array of household products. Results appear online in the journal Environmental Health Perspectives.
'Disease in a dish' approach could aid Huntington's disease discovery efforts
Creating induced pluripotent stem cells or iPS cells allows researchers to establish "disease in a dish" models of conditions ranging from Alzheimer's disease to diabetes.
More Oxidative Stress Current Events and Oxidative Stress News Articles