Redox Regulation by Intrinsic Species and Extrinsic Nutrients in Normal and Cancer Cells

Abstract

■ Abstract Cells in multicellular organisms are exposed to both endogenous oxidative stresses generated metabolically and to oxidative stresses that originate from neighboring cells and from other tissues. To protect themselves from oxidative stress, cells are equipped with reducing buffer systems (glutathione/GSH and thioredoxin/thioredoxin reductase) and have developed several enzymatic mechanisms against oxidants that include catalase, superoxide dismutase, and glutathione peroxidase. Other major extrinsic defenses (from the diet) include ascorbic acid, β-carotene and other carotenoids, and selenium. Recent evidence indicates that in addition to their antioxidant function, several of these redox species and systems are involved in regulation of biological processes, including cellular signaling, transcription factor activity, and apoptosis in normal and cancer cells. The survival and overall well-being of the cell is dependent upon the balance between the activity and the intracellular levels of these antioxidants as well as their interaction with various regulatory factors, including Ref-1, nuclear factor-κB, and activating protein-1.

Effect of glutathione on homo- and heterotropic cooperativity in cytochrome P450 3A4

“…Moreover, the GSH level in primary cultures of rat hepatocytes is reported to be 40 -60 nmol/10 6 cells [74,75], which is equivalent to a concentration of 8 -12 mM (calculated assuming the volume of a single hepatocyte cell equal to 4940 µm 3 [76]). This concentration is subject to substantial changes in response to various stimuli [41,48,73,77,78]. In particular, exposure of human hepatocarcinoma Hep2 cells to organochlorine insecticides, such as DDT, decreases the GSH concentration from 4 -5 down to 1.2 -1.5 mM (calculated from [48] assuming the protein content in hepatocytes to be of 220 mg/g [79]).…”

Health benefits of nuts: potential role of antioxidants

“…Dietary compounds with the ability to induce the production of endogenous antioxidants An important antioxidant defence mechanism involves detoxification enzymes such as catalase, several types of glutathione peroxidase and superoxide dismutase, the glutathione S-transferase family, g-glutamyl cysteine synthetase and NAD(P)H: quinone reductase (quinone reductase) (Fahey et al 1997;Talalay, 2000;McEligot et al 2005). Many of these enzymes are generally referred to as phase two enzymes because they catalyze the conversion of xenobiotics, mutagenic metabolites or their precursors to compounds that are more readily excreted.…”

“…The endogenous antioxidant defence, which is produced by cells themselves, consists of components such as glutathione, thioredoxin and various antioxidant enzymes. Mutations in genes coding for these peptides or proteins often lead to increased incidence of oxidative stress-related diseases as well as premature death (Dalton et al 2004;Selverstone et al 2005).In addition to endogenous antioxidant defence, it has been hypothesized that dietary components may also contribute to antioxidant defence either by providing redox active compounds that can directly scavenge or neutralize free radicals or other ROS and RNS, or by providing compounds that can induce the gene expression of the endogenous antioxidants (Blomhoff, 2005;Moskaug et al 2005).Dietary compounds with the ability to induce the production of endogenous antioxidants An important antioxidant defence mechanism involves detoxification enzymes such as catalase, several types of glutathione peroxidase and superoxide dismutase, the glutathione S-transferase family, g-glutamyl cysteine synthetase and NAD(P)H: quinone reductase (quinone reductase) (Fahey et al 1997;Talalay, 2000;McEligot et al 2005). Many of these enzymes are generally referred to as phase two enzymes because they catalyze the conversion of xenobiotics, mutagenic metabolites or their precursors to compounds that are more readily excreted.…”

Circulating oxidized low-density lipoproteins are associated with overweight, obesity, and low serum carotenoids in older community-dwelling women

“…Among subjects with LDL is a large particle that contains one apoB molecule and a large number of triacylglycerol, free cholesterol, cholesterol ester, and phospholipid molecules [9]. LDL contains carotenes and xanthophylls, the two major classes of carotenoids in humans, and carotenoids protect LDL against oxidation [10]. The carotenoid content of LDL has been shown to be strongly correlated with serum carotenoid concentrations [11,12].…”

“…LDL contains carotenes and xanthophylls, the two major classes of carotenoids in humans, and carotenoids protect LDL against oxidation [10]. The carotenoid content of LDL has been shown to be strongly correlated with serum carotenoid concentrations [11,12].…”