Cellular defense against oxidized low density lipoproteins and fibrillar amyloid beta in murine cells of monocyte origin with possible susceptibility to the oxidative stress induction.
Reactive oxygen species (ROS) are associated with aging and the correlation between Alzheimer's disease and atherosclerosis is a subject of the discussion. The aim of this study was to determine whether genetic factors affect cellular defense against cytotoxic beta-amyloid (Abeta) which is considered to be the source of ROS. Low levels of Abeta (1-10 microM) led to a significant suppression of redox potential as measured by MTT assay in bone marrow-derived cell lines. The atherosclerosis-resistant cells (GG2EE) were less affected than the susceptible cells (ANA1) in the time-, dose-, and Abeta species-dependent manner. Cell death in amyloid treated resident susceptible macrophages (C57BL/6J), measured by lactate dehydrogenase release, was induced during prolonged incubation and increased when compared with the resistant macrophages (C3H/HeJ, P = 0.005). SDS-PAGE showed that Abeta persisted intracellularly during this period. The cytotoxicity of oxidized low density lipoproteins (oxLDLs) significantly affected only the susceptible cells which actually lowered this cytotoxicity, thus, implying that the harmful effect of the oxLDLs was diminished when compared to that of Abeta. This fact demonstrates that in vitro the defense by cells of monocyte origin against Abeta may be determined in part genetically whereas the reaction to oxLDLs could be fully underlined by genetic susceptibility.
Ham
Daniela
D
Rideau Institute Advanced Research Centre for Physical and Behavioral Sciences, 4773 Sherbrooke West, Montreal H3Z 1G5, Canada. hamdaniela@yahoo.com
Skoryna
Stanley C
SC
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D013045:Species Specificity
D016229:Amyloid beta-Peptides; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein