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Research Newsletter-Fall/Winter 2010


The Oxygen Club of California held its biennial scientific conference—co-sponsored by LPI—in Santa Barbara, California, in mid-March. Oxidants and Antioxidants in Biology: Translational Redox Science featured 44 presentations in six sessions: Wound Healing; Redox Signaling and Inflammation; Cardiovascular; Translational Science by Micronutrients, which included subsessions on Carotenoids and Vitamin A, Coenzyme Q, and Polyphenols; Redox Imaging; and Aging. There was also a poster session with over 100 presentations covering an extraordinary range of topics.

The keynote lectures were given by two of the 2008 Nobel Laureates in Physiology or Medicine, Harald zur Hausen and Luc Montagnier. Zur Hausen won "for his discovery of human papilloma viruses causing cervical cancer" and Montagnier won, together with Françoise Barré-Sinoussi, "for their discovery of human immunodeficiency virus." In his presentation on "Novel infectious agents in human carcinogenesis: State and perspectives," zur Hausen discussed the potential effect of vaccinations on preventing cancers caused by hepatitis B virus and human papillomaviruses. He addressed the mechanism by which certain viruses can cause the transformation of normal cells to malignant cells, as well as the combined effects of viral infections, dietary factors, and other influences in that process. Montagnier talked about "New horizons in HIV/AIDS," including his development of novel technology to detect persistent reservoirs of HIV DNA in the blood of patients undergoing combined antiretroviral drug therapy.

Tissue injury triggers a number of responses that aid in healing. Speakers in the first session addressed this multifactorial response, which includes recruitment of repair signals and cells to the injury site stimulated by either hypoxia (reduced oxygen tension) in bone marrow or hyperbaric oxygen treatment, which also stimulates angiogenesis (new blood vessel formation) at the wound.

Speakers in the second session focused on redox (reduction "electron gain"—oxidation "electron loss") signaling and regulation, which play important roles in cellular metabolism, immune function, response to injury, inflammation, and cell growth. The balance between oxidants and endogenous antioxidants like thioredoxin, glutaredoxin, and peroxiredoxins controls, among other things, the fate of cells. In rats, resveratrol was shown to improve cardiac parameters, including stem cell performance, after coronary artery occlusion. In old rats, R-alpha lipoic acid improved antioxidant capacity in the liver not by acting itself as an antioxidant but rather by reversing age-related declines in the endogenous antioxidant glutathione. Redox imaging was discussed in the fifth session, with presentations on new instrumentation and molecular probes that provide imaging and measurements of reactive oxygen species in vivo.

In the third session on cardiovascular diseases, speakers explained how redox status affects diabetes-related impairment of angiogenesis after myocardial infarction in rats. Treatment with a virus containing the gene for the antioxidant thioredoxin improved outcomes. Thioredoxin also exhibits cardioprotective effects related to the growth and death of heart muscle cells. Oxysterols, the oxidized metabolites of cholesterol found in food and produced in the body, are associated with the development of atherosclerosis and could, because of their inflammatory potential, contribute to other diseases.

The Norman I. Krinsky Memorial Lecture focused on the metabolism of carotenoids. Norman Krinsky, who made seminal contributions to carotenoid research during a long and productive career at Tufts University, died in 2008. Carotenoids are colored compounds, some of which produce vitamin A and play important roles in eye health and immunity. Several speakers discussed genetic polymorphisms (variations) that probably account for the great variability among humans in carotenoid absorption and conversion. Indeed, intake of beta-carotene, which is converted into vitamin A, does not always predict vitamin A status. Vitamin A may also have an important effect on energy production in the mitochondria.

Coenzyme Q, which also plays an important role in the production of chemical energy in the mitochondria, may affect apoptosis (programmed cell death) and aging. Coenzyme Q reduces the age-related expression of oxidase enzymes that generate superoxide radicals, which are damaging reactive oxygen species. Treatment of astrocytes (glial cells in the central nervous system) in culture or human subjects with statins—drugs administered to lower cholesterol levels—substantially decreased coenzyme Q levels.

Inflammatory pathways that figure in chronic diseases may be modulated by certain dietary factors, including resveratrol and curcumin from the spice turmeric, as well as a host of other spices. In mice, resveratrol also shares similarities with caloric restriction in retarding aging (represented by gene analysis), especially in the heart.

Polyphenols from plants affect redox pathways, thereby increasing antioxidant and detoxification capacity. However, polyphenols like ellagitannins from pomegranates have very limited bioavailability—only very small amounts are absorbed into the blood stream from the gut—and are extensively and rapidly chemically modified after absorption. Therefore, it is difficult to extrapolate from cell culture studies to in vivo behavior and from parent compounds to their metabolic derivatives.

The last session focused on aging. Researchers showed that specially bred mice lacking the RasGrf1 gene involved in cognitive function and glucose homeostasis had an increased lifespan that mimicked the effect on lifespan by caloric restriction. Another speaker discussed the need for oxidized protein to be degraded and removed from cells; otherwise, protein aggregates can form that result in cellular senescence. Age-related dysfunction in vascular cells (the endothelium) caused by oxidative stress and inflammation is similar to endothelial changes observed in young people with diabetes or hypertension. The "triage theory" was advanced by Bruce Ames to explain how micronutrient deficiencies throughout evolution result in metabolic rebalancing to favor those substances required for short-term survival while starving those needed for long-term health. Chronic micronutrient deficiencies, which are prevalent even in apparently well-nourished societies, may contribute to the incidence of age-related disease.

Bharat Aggarwal of the M. D. Anderson Cancer Center of the University of Texas won the $25,000 Oxygen Club of California Jarrow Formulas Health Sciences Prize for his long-term work on the role of natural products, especially spices, in attenuating chronic inflammation associated with the development of cancer.

Based on their poster presentations, Jennifer Ehren of The Salk Institute for Biological Sciences and Ryan Hamilton of the University of Southern California won LPI Young Investigator Awards. Dr. Ehren showed that fisetin, a flavonoid in strawberries and other fruits, improved multiple physiological parameters, including nerve and kidney function, when fed to diabetic mice. Dr. Hamilton discussed findings showing that caloric restriction when young may help prevent hypometabolism and mitochondrial dysfunction associated with Alzheimer's disease when older.

Last updated November 2010