Science Current Events | Science News | Brightsurf.com
 

Scientists identify major source of cells' defense against oxidative stress

April 09, 2012

Research 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


High blood pressure linked to short-, long-term exposure to some air pollutants
Both short- and long-term exposure to some air pollutants commonly associated with coal burning, vehicle exhaust, airborne dust and dirt are associated with the development of high blood pressure, according to new research in the American Heart Association's journal Hypertension.

The deadly toxin acrolein has a useful biological role
Scientists from RIKEN in Japan have discovered that acrolein--a toxic substance produced in cells during times of oxidative stress--in fact may play a role in preventing the process of fibrillation, an abnormal clumping of peptides that has been associated with Alzheimer's disease and other neural diseases.

Ever-changing moods may be toxic to the brain of bipolar patients
Bipolar disorder (BD) is a severe and complex mental illness with a strong genetic component that affects 2% of the world population. The disorder is characterized by episodes of mania and depression that may alternate throughout life and usually first occur in the early 20s.

New study surveys genetic changes linked with Parkinson's disease
After Alzheimer's, Parkinson's disease (PD) is the leading neurodegenerative disorder, affecting close to a million Americans, with 50,000 new cases diagnosed every year. A progressive disorder of the nervous system affecting movement, PD typically strikes adults in mid-life.

Researchers identify genes linked to the effects of mood and stress on longevity
The visible impacts of depression and stress that can be seen in a person's face -- and contribute to shorter lives -- can also be found in alterations in genetic activity, according to newly published research.

Probiotic bacteria could provide some protection against cadmium poisoning
Oral administration of certain probiotics reduced uptake of the heavy metal, cadmium, in the intestines of mice, and in a laboratory experiment using human intestinal cells.

Altered purine metabolism linked to depression
People suffering from major depressive disorder may have altered purine metabolism, according to a new study from the University of Eastern Finland and Kuopio University Hospital.

Can sesame-based ingredients reduce oxidative stress?
The antioxidant boosting properties of sesame, and especially sesame oil, can have a significant effect on oxidative stress, improving human health, according to a systematic review published in Journal of Medicinal Food, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

New research shows sensitivity to oxidative stress is not always linked to aging
A study published in the US journal, Aging by the University of Surrey and University of Rochester has made an important breakthrough in understanding the impact of oxygen exposure on the aging process of mammal cells.

New computer program can help uncover hidden genomic alterations that drive cancers
Cancer is rarely the result of a single mutation in a single gene.
More Oxidative Stress Current Events and Oxidative Stress News Articles

Oxidative Stress and Antioxidant Protection: The Science of Free Radical Biology and Disease

Oxidative Stress and Antioxidant Protection: The Science of Free Radical Biology and Disease
by Donald Armstrong (Editor), Robert D. Stratton (Editor)


Oxidative Stress and Antioxidant Protection: The Science of Free Radical Biology and< Disease provides an overview of the basic principles of free radical formation. The text delves into free radical formation in molecular biology and its effect on subcellular damage, as well as the role of antioxidant reserves as a protective mechanism. Oxidative Stress and Antioxidant Protection begins with a historical perspective of pioneers in oxidative stress with an introductory section that explains the basic principles related to oxidative stress in biochemistry and molecular biology, demonstrating both pathways and biomarkers. This section also covers diagnostic imaging and differential diagnostics. The following section covers psychological, physiologic, pharmacologic and pathologic correlates....

Oxidative Stress: What is Oxidative Stress?

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.

How Not to Die: Discover the Foods Scientifically Proven to Prevent and Reverse Disease

How Not to Die: Discover the Foods Scientifically Proven to Prevent and Reverse Disease
by Michael Greger (Author), Gene Stone (Author)


From the physician behind the wildly popular website NutritionFacts.org, How Not to Die reveals the groundbreaking scientific evidence behind the only diet that can prevent and reverse many of the causes of disease-related death.The vast majority of premature deaths can be prevented through simple changes in diet and lifestyle. In How Not to Die, Dr. Michael Greger, the internationally-renowned nutrition expert, physician, and founder of NutritionFacts.org, examines the fifteen top causes of premature death in America-heart disease, various cancers, diabetes, Parkinson's, high blood pressure, and more-and explains how nutritional and lifestyle interventions can sometimes trump prescription pills and other pharmaceutical and surgical approaches, freeing us to live healthier lives.The...

Molecular Basis of Oxidative Stress: Chemistry, Mechanisms, and Disease Pathogenesis

Molecular Basis of Oxidative Stress: Chemistry, Mechanisms, and Disease Pathogenesis
by Frederick A. Villamena (Author)


Sets the stage for the development of better diagnostic techniques and therapeutics Featuring contributions from an international team of leading clinicians and biomedical researchers, Molecular Basis of Oxidative Stress reviews the molecular and chemical bases of oxidative stress, describing how oxidative stress can lead to the development of cancer and cardiovascular and neurodegenerative diseases. Moreover, it explains the potential role of free radicals in both the diagnosis and the development of therapeutics to treat disease. Molecular Basis of Oxidative Stress is logically organized, beginning with a comprehensive discussion of the fundamental chemistry of reactive species. Next, the book: Presents new mechanistic insights into how oxidative damage of biomolecules occurs Examines...

Inflammation, Aging, and Oxidative Stress (Oxidative Stress in Applied Basic Research and Clinical Practice)

Inflammation, Aging, and Oxidative Stress (Oxidative Stress in Applied Basic Research and Clinical Practice)
by Stephen C. Bondy (Editor), Arezoo Campbell (Editor)


The book describes the major degenerative processes and pathologies exacerbated by senescence and how they can be alleviated through retardation of cellular aging. Topics discussed include neurodegenerative disease, protein oxidation, cerebrovascular disease, particle-induced inflammation and cardiovascular disease, Alzheimer’s disease, ovarian aging, dietary and endogenous anti-oxidants in management of Parkinson’s disease, and effects of exercise on oxidation and inflammation. The nineteen expertly authored chapters are organized into three sections in order to present a complete picture to the reader: Age Related Cellular Events, Role of Inflammatory and Oxidative Processes in Age-Related Diseases, and Retardation of Cellular Aging.Inflammation, Oxidative Stress and Age-Related...

  Oxidative Stress Mechanisms and Their Modulation
by Mohinder Bansal (Author), Naveen Kaushal (Author)


Research over the years has demonstrated that free radicals mediated oxidative stress lies at the helm of almost all patho-physiological phenomena. These findings emphasize on the need to understand the underlying molecular mechanism(s) and their critical role in the pathogenesis. This book aims to focus on these areas to provide readers a comprehensive outlook about the major redox sensitive pathways and networks involved in various disease conditions. In the first chapter of the book, basic information about the oxidative stress, its generation, its biomarkers and its role in body are discussed. In the next three chapters, the role of oxidative stress in various pathologies ranging from neurological disorders, to cardiovascular diseases, cancers, metabolic diseases and ageing have been...

Studies on Veterinary Medicine (Oxidative Stress in Applied Basic Research and Clinical Practice)

Studies on Veterinary Medicine (Oxidative Stress in Applied Basic Research and Clinical Practice)
by Lester Mandelker (Editor), Peter Vajdovich (Editor)


This compendium of research material on the role of oxidative stress in animal disease and morbidity examines both the general and the specific. Sourced from scientists, veterinarians, and members of the medical community from around the world, it includes chapters on our wider understanding of the corrosive function of free radicals in cell biology as well as focusing on the interplay between oxidative stress and metabolism in a variety of animal species including dogs, ruminants and birds. Since biogerontologist Denham Harman first posited that free radicals arising from the metabolic activity of oxygen play a central role in aging and disease, a mass of evidence has accumulated linking oxidative stress and biological degradation. We now understand that living in an aerobic environment...

  Perinatal and Prenatal Disorders (Oxidative Stress in Applied Basic Research and Clinical Practice)
by Phyllis A. Dennery (Editor), Giuseppe Buonocore (Editor), Ola Didrik Saugstad (Editor)


This authoritative volume describes the role of free radicals and antioxidants in prenatal and perinatal disorders currently explored in clinical and pre-clinical trials. In twenty-two inclusive chapters, the book covers the gamut of oxidative stress and its relation to a variety of factors, including fertility, metabolism, redox biomarkers, antioxidant defense and protection, gene polymorphisms, angiogenesis, cell signaling, mutations and oxidative damage involving lipids, proteins and nucleic acids, membrane trafficking, inflammation, mitochondrial dysfunction, alterations in immunological function, hypoxia, and post-natal stressors. This comprehensive source will keep clinicians and research scientists up-to-date on translational research into medical applications. Perinatal and...

Redox-Active Therapeutics (Oxidative Stress in Applied Basic Research and Clinical Practice)

Redox-Active Therapeutics (Oxidative Stress in Applied Basic Research and Clinical Practice)
by Ines Batinic-Haberle (Editor), Julio S. Reboucas (Editor), Ivan Spasojevic (Editor)


This essential volume comprehensively discusses redox-active therapeutics, focusing particularly on their molecular design, mechanistic, pharmacological and medicinal aspects.  The first section of the book describes the basic aspects of the chemistry and biology of redox-active drugs and includes a brief overview of the redox-based pathways involved in cancer and the medical aspects of redox-active drugs, assuming little in the way of prior knowledge. Subsequent sections and chapters describe more specialized aspects of central nervous system injuries, neurodegenerative diseases, pain, radiation injury and radioprotection (such as of brain, lungs, head and neck and erectile function) and neglected diseases (e.g., leishmaniasis). It encompasses several major classes of redox-active...

Oxidative Stress: Diagnostics, Prevention, and Therapy Volume 2 (ACS Symposium Series)

Oxidative Stress: Diagnostics, Prevention, and Therapy Volume 2 (ACS Symposium Series)
by Maria Hepel (Editor), Silvana Andreescu (Editor)


This book provides a comprehensive overview of the oxidative stress related mechanisms in biological systems and the involvement of reactive oxygen and nitrogen species (ROS and RNS), the damage of DNA, proteins, and lipids caused by oxidative stress, the protection of cells and tissues against free radicals, the relation of the oxidative stress to aging and human diseases including cancer and neurological disorders, and the development of new therapeutic approaches to modulate oxidative stress. The current state-of-the-art methodologies including the development of sensors and biosensors for the detection of ROS/RNS and of biomarkers of oxidative stress are also discussed.

The book is organized in three overlapping parts, starting with general considerations of the oxidative...

© 2016 BrightSurf.com