Rex Michael Tyrrell

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The heme biosynthetic and catabolic pathways generate pro- and antioxidant compounds, and consequently, influence cellular sensitivity to oxidants. Heme precursors (delta-aminolevulinic acid, porphyrins) generate reactive oxygen species (ROS), from autoxidation and photochemical reactions, respectively. Heme, an essential iron chelate, serves in(More)
We have shown that UVA (320-380 nm) radiation, hydrogen peroxide, and sodium arsenite induce a stress protein of approximately 32 kDa in human skin fibroblasts. The synthesis and cloning of cDNA from arsenite-induced mRNA populations have now allowed us to unequivocally identify the 32-kDa protein as heme oxygenase. By mRNA analysis we have shown that the(More)
Accumulation of heme oxygenase mRNA is strongly stimulated by treatment of cultured human skin fibroblasts with ultraviolet radiation, hydrogen peroxide, or the sulfhydryl reagent sodium arsenite (S. M. Keyse and R. M. Tyrrell. Proc. Natl. Acad. Sci. USA, 86: 99-103, 1989). Since this will result in a transient reduction in the prooxidant state of cells,(More)
Solar UVB (290-320 nm) and particularly UVA (320-380 nm) radiations have a capacity to generate reactive chemical species, including free radicals, in cells. These intermediates have been shown to be involved in various biological effects in cultured human skin cells (e.g. cell death) and skin (e.g. erythema). Endogenous glutathione is a critical molecule(More)
The premutagenic oxidative DNA base damage, 7,8-dihydro-8-oxoguanine, is induced in human skin fibroblasts by monochromatic radiation ranging from a UVB wavelength (312 nm) up to wavelengths in the near visible (434 nm). The oxidative damage is not generated by absorption of radiation in DNA but rather by activation of photosensitizers generating genotoxic(More)
This study describes the damage that occurs to lipids and proteins that have been irradiated in vitro or in human skin fibroblasts with physiological doses of UVA radiation. Thiobarbituric acid-reactive species were formed from phosphatidylcholine after UVA radiation in vitro. By using iron chelators, this process was shown to involve iron. Ferric iron(More)
The aim of the present investigation was to determine whether an acute bout of exercise increases heme oxygenase-1 (HO-1) mRNA accumulation in human lymphocytes. Eight male subjects performed separate exercise and rest trials in a randomised order at least 10 days apart. In the exercise trial subjects ran for 75-min at a speed corresponding to 70% maximal(More)
In contrast to the immunosuppressive potential of UVB (280-320 nm) radiation in experimental animals and humans, UVA (320-400 nm) radiation at environmentally relevant doses appears to be immunologically inert. However, such exposure to UVA radiation has been observed unexpectedly to induce resistance to UVB-induced immunosuppression in mice, by a mechanism(More)
Regular exercise may improve systemic markers of chronic inflammation, but direct evidence and dose-response information is lacking. The objective of this study was to examine the effect and time course of changes in markers of chronic inflammation in response to progressive exercise training (and subsequent detraining). Forty-one sedentary men 45-64 yr of(More)