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dc.contributor.convenorProf. Evelyn Baumgart-Vogt
dc.contributor.authorDunner, Emily
dc.contributor.authorNewman, Judith
dc.contributor.authorWatters, Dianne
dc.description.abstractDunner EM, Newman JV and Watters DJ. School of Biomolecular and Physical Sciences and The Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Queensland, 4111, Australia. Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disease characterised by oxidative stress and cancer predisposition. Extensive research has characterised the DNA damage response role for nuclear ATM (ataxia-telangiectasia-mutated), the protein defective in A-T, however very little is known about the role of cytoplasmic ATM. In this study, novel mechanisms contributing to disease progression in A-T were investigated. We examined the endosomal recycling of membrane receptors for epidermal growth factor (EGF) and transferrin in control and A-T fibroblasts, as well as the cellular distribution of cholesterol and lipid droplets in control and A-T fibroblasts, and in astrocytes from wild-type and A-T mice. Transferrin and EGF remained localised to the perinuclear region in A-T fibroblasts, indicating defective recycling in A-T. Immunofluorescence studies showed partial colocalisation of transferrin with recycling endosome markers. Other cellular anomalies observed included increased intracellular cholesterol. Using the unesterified cholesterol-binding fluorescence antibiotic, filipin, a bright punctate intracellular staining pattern in cytoplasmic vesicles was revealed in the perinuclear region of A-T fibroblasts while minimal internal staining was seen in controls. Nile red labelling for lipid droplets indicated increased lipid droplets in A-T fibroblasts compared to controls. This was also observed in A-T astrocytes relative to wild-type. Treatment of control fibroblasts with hydrogen peroxide led to punctate cytoplasmic filipin staining and increased lipid droplets in the treated fibroblasts similar to that seen in A-T fibroblasts, suggesting that the increased lipid droplets and abnormal cholesterol distribution may be due to oxidative stress. We have also observed defective sphingolipid trafficking and mitochondrial abnormalities in A-T cells. All of these features could contribute to neurodegeneration in A-T.
dc.publisherJustus-Liebig University
dc.relation.ispartofconferencename102nd annual meeting of the Anatomische Gesellschaft
dc.relation.ispartofconferencetitleProceedings of the 102nd annual meeting of the Anatomische Gesellschaft
dc.relation.ispartoflocationGiessen, Germany
dc.titleCellular Defects in ataxia-telangiectasia
dc.typeConference output
dc.type.descriptionE3 - Conferences (Extract Paper)
dc.type.codeE - Conference Publications
gro.hasfulltextNo Full Text
gro.griffith.authorWatters, Dianne J.
gro.griffith.authorNewman, Judith V.
gro.griffith.authorDunner, Emily

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