Aluminum-induced apoptosis in cultured astrocytes and its effect on calcium homeostasis.
Aluminum exposure and apoptotic cell death has been implicated in several neurodegenerative conditions including Alzheimer's disease. In this study, we use cultured astrocytes to investigate the ability of aluminum to induce the apoptosis of astrocytes. The proportion of apoptotic cells and cell cycle distribution were determined by flow cytometric analysis. Our results showed that exposure to aluminum at low levels (100 and 200 microM) for up to 6 days did not result in the apoptosis of astrocytes, and a dramatic blockage of apoptotic cells was found at 200 microM aluminum. However, at 400 microM, aluminum markedly induced the apoptosis of astrocytes, which was associated with a significant change in cell cycle distribution characterized by increase of G2/M phase cells (128%). Measurements of intracellular Ca(2+) concentration using the fluorescent calcium indicator dye Fluo-3 demonstrated a significant increase in the levels of intracellular calcium after aluminum treatment. However, no differences were observed among aluminum-treated groups. These findings suggest that aluminum induce and block selectively the apoptosis of astrocytes, which depend upon the concentrations of aluminum. Increased intracellular Ca(2+) may not be the primary mechanism of aluminum-mediated apoptotic cell death.
Guo
G W
GW
2nd Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 294 Taiyuan Road, 200031, Shanghai, PR China. gwguo@21cn.com
Liang
Y X
YX
D000535:Aluminum / Q000633:toxicity*; D000814:Aniline Compounds; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D006706:Homeostasis / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time; D014966:Xanthenes
D000814:Aniline Compounds; D005456:Fluorescent Dyes; D014966:Xanthenes; C059715:Fluo-3; D000535:Aluminum; D002118:Calcium