Co-toxicity of ATP and menadione, effects on intracellular calcium regulation in hepatocytes

dc.contributor.authorFisher, Candace E.en_US
dc.date.accessioned2007-05-18T19:59:16Z
dc.date.available2007-05-18T19:59:16Z
dc.date.issued1999-08-01T00:00:00Zen_US
dc.degree.disciplinePharmacology and Therapeuticsen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractThe effects of non-lethal oxidative stress on cytosolic calcium regulation in hepatocytes are inadequately understood. It was hypothesized that non-lethal oxidative stress and calcium mobilizing agonists are co-toxic and that non-lethal oxidative injury would result in impaired responsiveness to receptor mediated-calcium mobilization. 'Methods'. Oxidative injury was induced in a dose-dependent manner in cultured hepatocytes using the prooxidant chemical, menadione. A lethal (100[mu]M) and a non-lethal (10[mu]M) dose of menadione were defined. Co-toxicity of the calcium-mobilizing purinergic receptor agonist, ATP, and the effects of menadione on ATP-related calcium signaling were determined by incubating hepatocytes for 2 hours with menadione and then exposing hepatocytes to normally non-toxic concentrations of ATP. A propidium iodide exclusion assay was used to assess for cell necrosis. Nuclear stains with Hoechst 33258 and a fluorescein-based TUNEL assay were used to assess apoptosis. Cytosolic free calcium was evaluated using Fura-2-AM. (Abstract shortened by UMI.)en_US
dc.format.extent2586126 bytes
dc.format.extent184 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.identifier.urihttp://hdl.handle.net/1993/1803
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.titleCo-toxicity of ATP and menadione, effects on intracellular calcium regulation in hepatocytesen_US
dc.typemaster thesisen_US
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