Atherosclerosis is the underlying cause of ischemic heart disease and stroke and is the leading cause of death worldwide, especially in developed countries. As an inflammatory disease of arteries in a hyperlipidemic milieu, expression of adhesion molecules, such as endothelial-leukocyte adhesion molecule-1 (E-selectin) and intercellular adhesion molecule-1 (ICAM-1), on endothelial...
Oxidative stress is the major driving force behind the aging process and many age-related diseases. However, direct experimental evidence of whether antioxidants, such as ascorbate (AA) and lipoic acid (LA) can slow the progression of aging process and/or reduce risks of developing degenerative disease is largely absent. This suggests a...
The recommended dietary allowance (RDA) of vitamin C has traditionally been based on the prevention of the vitamin C deficiency disease, scurvy. While higher intakes of vitamin C may exert additional health benefits, the limited Phase III randomized placebo-controlled trials (RCTs) of vitamin C supplementation have not found consistent benefit...
Vitamin C is an essential component of the human diet. Uptake of vitamin C in the cell is regulated by the function of sodium-dependent vitamin C transporters (SVCTs). SVCT1 (encoded by the SLC23A1 gene) is expressed in the colon, liver and kidney, where it plays a vital role in determining...
Ceramides are a group of lipids in the sphingolipid family that are potent cell signaling molecules. Elevations in ceramide levels above the norm generally lead to apoptosis. Evidence from in vitro studies suggests that accumulation of ceramides within mitochondria leads to dysfunction of the mitochondria. This includes inhibition of the...
Nuclear Factor, Erythroid Derived 2, Like 2 (NFE2L2 or Nrf2) is the primary transcription factor in cellular defense against oxidative and xenobiotic stresses in higher eukaryotes. This basic leucine zipper transcription factor regulates over 200 antioxidant, detoxification, and lipid metabolizing genes by binding to the Antioxidant Response Element (ARE; a...
Decline in cardiac pump function is a hallmark of aging where mitochondrial decay is an important underlying cause. Although certainly multifactorial in nature, both dysfunction of the machinery involved in the chemiosmotic process of energy transduction and lower capacity to maintain fatty acid-driven respiration are identified as intrinsic factors of...
Aerobic organisms have evolved many sensory mechanisms that allow
response to oxidants in the environment. One area of interest is the relationship
between the activity of the tumor suppressor protein p53 and the redox state of
thioredoxin. Human p53 activity is severely compromised in budding yeast lacking
thioredoxin reductase. Evidence...
Mutations to superoxide dismutase were the first proven cause of Lou
Gehrig’s disease (amyotrophic lateral sclerosis; ALS) implicating superoxide in
the selective death of motor neurons that characterizes ALS. Nitric oxide
competes effectively with superoxide dismutase for superoxide to form the
powerful oxidant peroxynitrite. Endogenous formation of peroxynitrite can kill...