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SHR Neuro Krebs Kardio Lipid

Semlitsch, M; Shackelford, RE; Zirkl, S; Sattler, W; Malle, E.
ATM protects against oxidative stress induced by oxidized low-density lipoprotein.
DNA Repair (Amst). 2011; 10(8):848-860 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kickmaier Sandra
Malle Ernst
Sattler Wolfgang
Semlitsch Michaela
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Number of Figures: 10
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Abstract:
Chronic oxidative stress is involved in the pathogenesis of multiple inflammatory diseases, including cardiovascular disease and atherosclerosis. The rare autosomal recessive disorder Ataxia-telangiectasia (A-T) is characterized by progressive cerebellar ataxia secondary to Purkinje cell death, immunodeficiency, and increased cancer incidence. ATM, the protein mutated in A-T, plays a key role in cellular DNA-damage responses. A-T cells show poor cellular anti-oxidant defences and increased oxidant sensitivity compared to normal cells, and ATM functions, in part, as an oxidative stress sensor. The oxidation of low-density lipoprotein (oxLDL) and its uptake by macrophages is an initiating step in the development of atherosclerosis. We demonstrate that oxLDL activates ATM and downstream p21 expression in normal fibroblasts and endothelial cells. In ATM-deficient fibroblasts oxLDL induces DNA double-strand breaks, micronuclei formation and causes chromosome breaks. Furthermore, oxLDL decreases cell viability and inhibits colony formation in A-T fibroblasts more effectively as compared to normal controls. Formation of oxLDL-induced reactive oxygen species is significantly higher in A-T, than normal fibroblasts. Last, pre-treatment of cells with ammonium pyrrolidine dithiocarbamate, a potent antioxidant and inhibitor of transcription factor nuclear factor κB, reduces oxLDL-induced reactive oxygen species formation. Our data indicates that ATM functions in the defence against oxLDL-mediated cytotoxicity.
Find related publications in this database (using NLM MeSH Indexing)
Antioxidants - pharmacology
Ataxia Telangiectasia Mutated Proteins -
Cell Cycle Proteins - antagonists & inhibitors
Cell Line -
Cell Survival -
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
DNA Breaks, Double-Stranded -
DNA-Binding Proteins - antagonists & inhibitors
Endothelial Cells - drug effects
Fibroblasts - drug effects
Gene Expression -
Humans -
Lipoproteins, LDL - metabolism
Oxidative Stress -
Phosphorylation -
Protein Kinase Inhibitors - pharmacology
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Pyrrolidines - pharmacology
Reactive Oxygen Species - metabolism
Thiocarbamates - pharmacology
Tumor Suppressor Proteins - antagonists & inhibitors

Find related publications in this database (Keywords)
ROS
Modified LDL
DNA-double-strand breaks
Atherosclerosis
p21
Colony forming efficiency assay
EA.hy926 cells
Hydrogen peroxide
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