radical mechanisms in COX-catalyzed peroxidation of AA vs. DGLA correspond to their contrasting bioactivity. Supported NIH grants: R15CA140833 and P20RR015566.
doi:10.1016/j.freeradbiomed.2011.10.149
124 Estrogen Receptors and the Mitochondrial Antioxidant Enzyme Manganese Superoxide Dismutase Are Two Key Players in the Cellular Activities of Phytoestrogens Ellen Robb1, and Jeff Stuart1 1 Brock University Dietary phytoestrogens have well documented effects on human health; however, the cellular mechanisms responsible are not well understood. Two properties that are important in the context of cancer and neurodegenerative diseases are the rate of cell division and the ability of cells to withstand stress. Our previous work with the phytoestrogen resveratrol (RES) revealed that its ability to slow cell growth and increase stress resistance is dependent on an increase in the antioxidant enzyme manganese superoxide dismutase (MnSOD). This effect can be inhibited with an estrogen receptor antagonist and mimicked with an estrogen receptor beta (ERβ ) agonist. Both MnSOD and ERβ activation are associated with slower rates of cell proliferation and increased stress resistance in a number of experimental contexts. We hypothesize that RES’s effects are mediated through ERβ and MnSOD, and that the same mechanism is shared by other phytoestrogens and RES derivatives. We examined the ability of estradiol, diethylstilbestrol, coumestrol, kaempferol, glycitein, genistein, daidzein, and the RES derivatives piceid, pterostilbene, resveratrol-3-sulfate or resveratrol-3glucuronide, to affect MnSOD, rates of cell division and stress resistance in cultured mouse myoblasts. To clarify the role of specific estrogen receptors in the phytoestrogen effects we used ERα and ERβ specific agonists, antagonists, and ERβ null fibroblasts and myoblasts. We extended our in vitro investigation of estrogen receptors and antioxidant enzymes to heart, brain and liver tissue of ERβ null mice. Surprisingly, we observed changes in rates of cell division, stress resistance or MnSOD with many of the phytoestrogens tested, excluding glycitein and pterostilbene. the metabolites resveratrol3-sulfate and resveratrol-3-glucuronide did not affect the measured parameters. When we treated myoblasts with estradiol, genistein, daidzein or coumestrol and prevented the increase in MnSOD, we found that the effects on population doubling time or stress resistance were eliminated, supporting the requirement of MnSOD in their mechanism of action. Our experiments explore an exciting mechanism of action of phytoestrogens that involves MnSOD and estrogen receptors.
can cross the blood–brain barrier and exhibits a neuroprotective effect. the administration of theanine reduces stress response and enhances cognitive functions. in the present study, we determined the level of theanine in the roots of tea plants cultured by nutrient solution. the concentration of theanine in the roots measured by HPLC was four times higher than the leaf. We determined the radical scavenging activity of the extract of tea roots by reduction of a stable radical DPPH. Results showed that the extract of roots containing theanine exhibited a high radical scavenging activity. To elucidate a functional significance of theanine, we examined the effect of theanine on memory impairments observed in aged rats (18 mo old). Whereas aged rats exhibited memory deficits in the delayed non-matching to a sample task, the oral administration of the extract of tea roots to aged rats attenuated this deficit. These results provide evidence of the beneficial effect of theanine on the brain function.
doi:10.1016/j.freeradbiomed.2011.10.151
126 The lost of Scavenger Receptor B1 by Cigarette Smoke Exposure in Keratinocytes is Driven by H2O2
Giuseppe Valacchi1, Claudia Sticozzi2, Alessandra Pecorelli3, Giuseppe Belmonte4, Emanuela Maioli5, Beatrice Arezzini3, and Concetta Gardi3 1 2 Dept. of Evolutionary Biology, Dept. di Ingegneria Meccanica e 3 4 Strutturale, Dept of Pathology, Dept of Biomedical 5 Sciences, Dept of Physiology, University of Siena Scavenger Receptor B1 (SRB1), also known as HDL receptor, is involved in cellular cholesterol uptake. Stratum corneoum (SC), the outermost layer of the skin, is composed for more than 25% by cholesterol. Several reports support the view that alteration of SC lipids composition may be the cause of impaired barrier function which gives rise to several skin diseases. for this reason the regulation of the genes involved in cholesterol uptake is of extreme significance for skin health. Being the first shield against the outdoor insults, the skin is exposed to several noxious substances and among these is cigarette smoke (CS) which has been recently associated to various skin pathologies. Using immunoblotting, immunoprecipitation, RT-PCR, and confocal microscopy we have demonstrated that the translocation and the consecutive lost of SRB1 in human keratinocytes after CS exposure is driven by hydrogen peroxide (H2O2) which derives not only from the CS gas phase but mainly from the activation of cellular NADPH oxidase (NOX). This effect was reversed when the cells were pretreated with NOX inhibitors, catalase, or superoxide dismutase (SOD) inhibitor. Furthermore, CS caused the formation of SRB1-aldheydes adducts (Acrolein and 4Hydroxynonenal) and the increased of its ubiquitination which is the cause of SRB1 lost. in conclusion, exposure to CS, through the production of H2O2, induced post-translational modifications of SRB1 with the consequence lost of the receptor and this may contribute to the skin physiology alteration.
doi:10.1016/j.freeradbiomed.2011.10.150 doi:10.1016/j.freeradbiomed.2011.10.152
125 127 Theanine in the Tea Roots Attenuates Memory Deficits in the Aged Rats Kieko Saito1, Masahiko Ikeda2, and Hideki Kametani3 1 2 3 University of Shizuoka, Fuji Tokoha University, Saitama Institute of Technology Theanine (N-ethyl-L-glutamine) is one of various amino acids found in green tea. Theanine is synthesized in the tea roots and transferred to the leaves. It is easily absorbed by the intestine and
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Lack of Nrf2 Reduces Voluntary Exercise in Mice: Influences of Sex and Diet Emilie Erin Vomhof-DeKrey1, and Matthew J. Picklo Sr.1,2 1 2 USDA-ARS, Dept. of Pharmacology, Physiology, & Therapeutics, University of North Dakota Exercise is generally accepted to increase the generation of reactive oxygen species (ROS). However, the regulatory
SFRBM 2011