GD3 accumulation in cell surface lipid rafts prior to mitochondrial targeting contributes to amyloid-ß-induced apoptosis.

Neuronal apoptosis induced by amyloid ß-peptide (Aß) plays an important role in the pathophysiology of Alzheimer's disease (AD). However, the molecular mechanism underlying Aß-induced apoptosis remains undetermined. The disialoganglioside GD3 involves ceramide-, Fas- and TNF-α-mediated apoptosis in lymphoid cells and hepatocytes. Although the implication of GD3 has been suggested, the precise role of GD3 in Aß-induced apoptosis is still unclear. Here, we investigated the changes of GD3 metabolism and characterized the distribution and trafficking of GD3 during Aß-induced apoptosis using human brain-derived TE671 cells. Extracellular Aß-induced apoptosis in a mitochondrial-dependent manner. GD3 level was negligible in the basal condition. However, in response to extracellular Aß, both the expression of GD3 synthase mRNA and the intracellular GD3 level were dramatically increased. Neosynthesized GD3 rapidly accumulated in cell surface lipid microdomains, and was then translocated to mitochondria to execute the apoptosis. Disruption of membrane lipid microdomains with methyl-ß-cyclodextrin significantly prevented both GD3 accumulation in cell surface and Aß-induced apoptosis. Our data suggest that rapidly accumulated GD3 in plasma membrane lipid microdomains prior to mitochondrial translocation is one of the key events in Aß-induced apoptosis.

Improvement of cardiac function and remodeling by transplanting adipose tissue-derived stromal cells into a mouse model of acute myocardial infarction.

BACKGROUND: We investigated the effect of adipose tissue-derived stromal cells (ADSC) therapy on cardiac contractility and remodeling in the C57BL/6 mouse model of acute myocardial infarction (AMI). METHODS: 30 adult male C57BL/6 mice were randomized into 2 groups, namely, AMI+media (control, n=15) and AMI+ADSC (n=15). AMI was produced by left anterior descending coronary artery ligation. After AMI induction, 1 x 10(6) ADSC or media were intramyocardially injected and the results compared. Echocardiographic and histological analyses of surviving mice (n=20) were conducted. Echocardiography was performed before cell implantation and 2 weeks after transplantation. RESULTS: LVEF and FS improved in the ADSC group compared to the control (P<0.01). LVEDD in the ADSC group decreased slightly from 4.65+/-0.63 mm to 4.14+/-0.53 mm compared to the control, but there was no statistical difference (P=0.072). LVESD decreased significantly in the ADSC group (P<0.05). A significant difference in scar formation and infarct size was observed between the ADSC and control group 2 weeks after AMI (P<0.05). ADSC were observed to migrate into injured sites and integrate into scar areas and increased vascular density in the infarct site compared to control group (P<0.05). Additionally, some transplanted ADSC expressed the endothelial marker. CONCLUSIONS: Echocardiography and histological analysis revealed that improvement in cardiac function and ventricular remodeling was better in the ADSC group than in the control. This suggests that ADSC is a good candidate for cell therapy in cardiovascular disease.