 |
Scientists identify major source of cells' defense against oxidative stress
April 09, 2012Research on how cells cope with stress could lead to more effective ways to weaken and kill cancer cells
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
Effect of different oxygen saturation levels on death or disability in extremely preterm infants
In a randomized trial performed to help resolve the uncertainty about the optimal oxygen saturation therapy in extremely preterm infants, researchers found that targeting saturations of 85 percent to 89 percent compared with 91 percent to 95 percent had no significant effect on the rate of death or disability at 18 months.
Mild blast injury causes molecular changes in brain akin to Alzheimer, Pitt team says
A multicenter study led by scientists at the University of Pittsburgh School of Medicine shows that mild traumatic brain injury after blast exposure produces inflammation, oxidative stress and gene activation patterns akin to disorders of memory processing such as Alzheimer's disease.
Women with HIV shown to have elevated resting energy expenditure
Studies have shown that about 10 percent of men infected with human immunodeficiency virus (HIV) have an elevated resting energy expenditure (REE).
Clues to heart disease in unexpected places, Temple researchers discover
A major factor in the advance of heart disease is the death of heart tissue, a process that a team of scientists at Temple University School of Medicine's (TUSM) Center for Translational Medicine think could be prevented with new medicines.
Cell-destroyer that fights and promotes TB reveals what's behind its split identity
Tumor necrosis factor - normally an infection-fighting substance produced by the body- can actually heighten susceptibility to tuberculosis if its levels are too high.
Neuron loss in schizophrenia and depression could be prevented with an antioxidant
Gamma-aminobutyric acid (GABA) deficits have been implicated in schizophrenia and depression. In schizophrenia, deficits have been particularly well-described for a subtype of GABA neuron, the parvalbumin fast-spiking interneurons.
Discovery of 'executioner' protein opens door to new options for stroke ALS, spinal cord injury
Oxidative stress turns a protein that normally protects healthy cells into their executioner, according to a study released today in the Proceedings of the National Academy of Sciences journal.
Losing weight sooner has best chance to reverse heart damage, mouse study shows
Johns Hopkins research on obese mice finds that the impact of dieting and losing weight benefits the heart health of the young, but not the older ones
Grape seed and skin extract - a weapon in the fight against kidney disease caused by high-fat diets
New insight into grape seed extract as a therapeutic and preventative measure to fight obesity-induced kidney damage is presented in a new study.
Activation of cortical type 2 cannabinoid receptors ameliorates ischemic brain injury
A new study published in the March issue of The American Journal of Pathology suggests that cortical type 2 cannabinoid (CB2) receptors might serve as potential therapeutic targets for cerebral ischemia.
More Oxidative Stress Current Events and Oxidative Stress News Articles
 |
Oxidative Stress: What is Oxidative Stress? by Matthew Jordan (Author) The term oxidative stress has been linked to multiple diseases and aging. Oxidative stress and managing free radicals through antioxidants has also become big business and it is important that consumers educate themselves on effective oxidative stress management. This book will provide a simple definition of oxidative stress along with sources of oxidative stress management. |
 |
Free Radicals in Biology and Medicine by Barry Halliwell (Author), John Gutteridge (Author) Free Radicals in Biology and Medicine has become a classic text in the field of free radical and antioxidant research since its first publication in 1985. This latest edition has been comprehensively rewritten and updated (over 80% of the text is new), while maintaining the clarity of its predecessor. There is expanded coverage of isoprostanes and related compounds, mechanisms of oxidative damage to DNA and proteins (and the repair of such damage), the free radical theory of aging and the roles played by reactive species in signal transduction, cell death, human reproduction, and other important biological events. Greater emphasis has also been placed on the methods available to measure reactive species and oxidative damage (and their potential pitfalls), as well as the importance... |
 |
Inflammation, Lifestyle and Chronic Diseases: The Silent Link (Oxidative Stress and Disease) by Bharat B. Aggarwal (Editor), Sunil Krishnan (Editor), Sushovan Guha (Editor) Oxidative stress and inflammation are among the most important factors of disease. Chronic infections, obesity, alcohol and tobacco usage, radiation, environmental pollutants, and high-calorie diets have been recognized as major risk factors for a variety of chronic diseases from cancer to metabolic diseases. All these risk factors are linked to chronic diseases through inflammation. While short-term, acute inflammation generated by the immune system serves a therapeutic role, chronic low-level inflammation that may persist "silently" for decades is responsible for chronic diseases. Inflammation, Lifestyle, and Chronic Diseases: The Silent Link describes the role of dysregulated inflammation in persistent and recurring diseases. It investigates links to lifestyle and presents research... |
 |
Oxidative Stress, Inflammation, and Health (Oxidative Stress and Disease) by Young-Joon Surh (Editor) Specifically focusing on the redox regulation of cell signaling responsible for oxidative stress and inflammatory tissue damage, this reference provides a comprehensive overview of cutting-edge research on the intracellular events mediating or preventing oxidative stress and pro-inflammatory processes induced by endogenous and xenobiotic factors-analyzing the implications of oxidative stress and inflammatory damage in the pathogenesis of human disorders such as cancer, neurodegenerative disease, and diabetes. |
 |
Adipose Tissue and Inflammation (Oxidative Stress and Disease) by Atif B. Awad (Editor), Peter G. Bradford (Editor) The American Obesity Association identifies obesity’s link to numerous medical conditions, including hypertension, type 2 diabetes, cardiovascular disease, several cancers, and a host of inflammatory disorders. Evidence indicates that inflammation has more than a corollary relation with obesity; that in fact, obesity itself manifests a low-grade, metabolically associated inflammation involving many of the same mediators associated with classic inflammation. Concurrent with our understanding, we have to recognize that more than a storage site for fat, adipose tissue itself is an essential endocrine organ that produces and secretes a host of hormones in response to varying physiologic and pathologic states. Bringing together the research and findings of leading experts from across... |
 |
Vitamin D: Oxidative Stress, Immunity, and Aging (Oxidative Stress and Disease) by Adrian F. Gombart (Editor) Vitamin D deficiency is a worldwide public health problem in both developed and developing nations. This book focuses on the role of vitamin D in three areas: oxidation, immunity and aging. The text presents new information on the action of vitamin D in regulating numerous aspects of health, disease, and aging. The author addresses the molecular and cellular mechanism responsible for the benefits of vitamin D and discusses the role of vitamin D in oxidative stress, including cancer, the nervous system, stress-mediated diseases, photoprotection, and energy metabolism, as well in the regulation of the aging process and its impact on diseases of aging, mortality, cardiovascular disease, and inflammation. |
 |
Oxidative Stress, Disease and Cancer by Keshav K. Singh (Editor) This book aims to provide a comprehensive review of the most up-to-date knowledge of the sources and molecular mechanisms of oxidative stress, and its role in disease and cancer. It also focuses on the novel agents and methods that can be employed to prevent oxidative stress and associated diseases. The authors first review the most recent data on the basic mechanisms of oxidative stress. The second section discusses oxidative stress leading to several diseases and cancers, and in the third section, the strategies employed in the prevention and treatment of oxidative stress-related diseases are discussed. |
 |
Antioxidants: Natural Defense Against Oxidative Stress (Woodland Health) by MPH Barbara Wexler (Author) Surprisingly, one of the most essential elements for human life-oxygen-is also responsible for cellular deterioration, aging, and many diseases. But nature has provided substances in our food called antioxidants to help keep oxygen from damaging cells and causing disease. Many antioxidants can be found in fresh fruits and vegetables, and vitamins A, C, and E are familiar types. In this helpful booklet, noted epidemiologist Barbara Wexler, MPH, further explains the process of oxidative stress in the body, discusses many different types of antioxidants and their sources, and explains how you can increase your antioxidant intake for a healthier life. |
 |
Oxidative Stress and Cardiac Failure by Marrick Kukin (Editor), Valentin Fuster (Editor) Far from being a direct complication of primary damage to heart muscle, it is now recognised that the pathogenesis of heart failure may rely on a combination of neurohormonal, cellular and molecular factors. An overwhelming number of systems appear to be activated in heart failure and contribute in some way towards structural remodelling.Comprising a comprehensive evaluation of the experimental and clinical data relating oxidative stress and heart failure, this text proposes that oxidative stress may be the common pathway for muscle dysfunction, cellular growth and remodelling, and mytocyte death. Acknowledged experts in the field here present a persuasive argument for raising the profile of oxidative stress as an important, perhaps critical contributor to the adverse consequences of... |
|
Oxidative Stress and Aging:: From Chemistry to Human Dietary Supplements (Aging Medicine) by Hoshi Toshinori (EDT)/ Pignolo Robert J. (EDT)/ Heinemann Stefan H. (EDT) (Author) |
| © 2013 BrightSurf.com |