The effects of oxidative stress and altered intracellular calcium levels on vesicular transport of apoE-EGFP.
Apolipoprotein E (apoE) plays a role in the distribution of lipid within many organs and cell types in the human body, including the central nervous system (CNS). The apoE4 isoform is also an established risk factor for late-onset Alzheimer's disease (AD), however its role in the aetiology of the disease remains largely unknown. Therefore, as AD is a late-onset disease, we sort to investigate how conditions hypothesised to model ageing affect apoE metabolism, such as the transport of apoE along the secretory pathway. Two of these models include oxidative stress and calcium deregulation. Using apoE-EGFP-expressing astrocytoma cell lines we established that vesicle number and velocity are up-regulated under oxidative stress conditions, and slowed under KCl induced calcium deregulation. Although these findings apply to cells in general under these two stress conditions, the up-regulation of apoE in particular may be a response to cell injury with implications for neurodegeneration such as that found with late-onset AD.
Dekroon
Robert M
RM
Neuroscience Unit, School of Biological Sciences A08, University of Sydney, NSW, 2006, Australia.
Armati
Patricia J
PJ
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D022162:Cytoplasmic Vesicles; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D017239:Paclitaxel / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D013997:Time Factors; D014407:Tumor Cells, Cultured
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008164:Luminescent Proteins; D016877:Oxidants; D020033:Protein Isoforms; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D002122:Calcium Chloride; D017239:Paclitaxel; D015739:Nocodazole; D002118:Calcium