Peter J O'brien

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The fast-paced development of nanotechnology needs the support of effective safety testing. We have developed a screening platform measuring simultaneously several cellular parameters for exposure to various concentrations of nanoparticles (NPs). Cell lines representative of different organ cell types, including lung, endothelium, liver, kidney,(More)
Bovine retinal rod outer segments (ROS) support the incorporation of [3H]palmitate into rhodopsin. [14C] Palmitoyl-CoA serves as the donor with an apparent Km of 40 microM. Solubilization of ROS in the detergent, Emulphogene, results in increased incorporation of label into rhodopsin. A further increase is found when ConA-Sepharose-purified rhodopsin is(More)
The antioxidant properties of the dietary dihydroxycinnamic acids [caffeic (CA), dihydrocaffeic (DHCA), and chlorogenic (CGA) acids] have been well studied but little is known about their metabolism. In this article, evidence is presented showing that CA, DHCA, and CGA form quinoids and hydroxylated products when oxidized by peroxidase/H(2)O(2) or(More)
Reactive oxygen species have been implicated in the pathogenesis of hypoxia-reoxygenation injury. Previously, we demonstrated that 2:1 catecholic iron complexes were more effective than uncomplexed catechols at (a) scavenging superoxide radicals generated enzymatically, and (b) protecting hepatocytes against hypoxia-reoxygenation injury [25]. Based on these(More)
Rat retinas were labeled by incubation with, or intravitreal injection of, [14C]leucine along with tritiated palmitic acid, glucosamine or galactose. At selected intervals, subcellular fractions were prepared on linear sucrose gradients and rhodopsin was extracted and purified by affinity chromatography and gel electrophoresis. Time courses revealed that(More)
Ascorbate is an important antioxidant in the brain. Astrocytes are capable of recycling ascorbate by taking up and then reducing its oxidation product dehydroascorbic acid (DHAA) using reducing equivalents derived from NAD(P)H. Astrocytes also contain NAD(P)H-dependent quinone reductases, such as NAD(P)H:quinone oxidoreductase (NQO1), which are capable of(More)
Free-radical metabolites can be generated metabolically by a one-electron reductase-catalyzed reaction or a "peroxidase" catalyzed oxidation or by photoactivation of a wide variety of aromatic xenobiotics. Radicals may also be generated during lipid peroxidation. Some radicals can react with DNA or bind covalently or noncovalently as a dismutation product(More)
A tyrosinase-directed therapeutic approach for treating malignant melanoma uses depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical trial, both renal and hepatic toxicity were reported as side effects of 4-HA therapy. In the following, 4-HA (200 mg/kg(More)
Azathioprine (AZA) is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using "Accelerated Cytotoxicity(More)
Rat retinas were incubated with [3H] palmitate and [14C] leucine and subsequently detergent-extracted. Glycoproteins were isolated on Con A-Sepharose columns and separated by gel electrophoresis. Leucine labeled the newly synthesized opsin but palmitate was esterified to both mature rhodopsin and newly synthesized opsin which migrated more slowly because of(More)