Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol—Implications for Niemann-Pick C1, Alzheimer’s Disease, and Atherosclerosis
Figure 3
Lipoprotein treatment induces aneuploidy.
(A) Actively growing hTERT-HME1 cells were treated with 20 µg/ml of OX-LDL, LDL or HDL for 48 hr, arrested in metaphase and Giemsa stained for karyotype analysis. All lipids induced significantly higher levels of aneuploidy compared to untreated cells, with LDL and or OX-LDL exhibiting a much stronger aneugenic effect than HDL. (B–E) FISH analysis of the same lipoprotein-treated cells showed that OX-LDL-induced trisomy 21 and trisomy 12 (B,D), and that both OX-LDL and LDL-induced tetrasomy 21 and 12 (C,E). (F) Karyotype analysis of an aliquot of the cells from the same treatment showed very few, but equal numbers of polyploid cells, indicating that the tetrasomies observed are due to chromosome mis-segregation of chromosomes 21 or 12, and not a result of chromosome duplication before cell division.