Distinct mechanisms account for beta-amyloid toxicity in PC12 and differentiated PC12 neuronal cells.
Whether reactive oxygen species (ROS) mediate beta-amyloid (A beta) neurotoxicity remains controversial. Naive PC12 cells (PC12) and nerve growth factor-differentiated PC12 cells (dPC12) were used to study the role of ROS in cell death induced by A beta(25-35). The viability of PC12 and dPC12 cells decreased by 30-40% after a 48-hour exposure to 20 microM A beta(25-35). Microscopic examination showed that A beta(25-35) induced necrosis in PC12 cells and apoptosis in dPC12 cells. Vitamin E (100 microM) and other antioxidants protected PC12 cells, but not dPC12 cells, against the cytotoxic effect of A beta(25-35). Since H(2)O(2) has been proposed to be involved in A beta toxicity, the effects of H(2)O(2) on PC12 and dPC12 cells were studied. Differentiated PC12 cells appeared to be significantly more resistant to H(2)O(2) than naive PC12 cells. These data suggest that ROS may mediate A beta(25-35) toxicity in PC12 cells but not in dPC12 cells. Because the intracellular levels of ROS were elevated during the differentiation of PC12 cells, the baseline levels of ROS in these two model cell types may determine the intracellular mediators for A beta(25-35) toxicity. Therefore, the protective effects of antioxidants against A beta may depend upon the redox state of the cells.
Sung
Yen-Jen
YJ
Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Cheng
Chia-lo
CL
Chen
Chaio-Sung
CS
Huang
Hsien-Bin
HB
Huang
Fong-Lee
FL
Wu
Pei-Chun
PC
Shiao
Ming-Shi
MS
Tsay
Huey-Jen
HJ
D000682:Amyloid; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D009336:Necrosis; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018384:Oxidative Stress; D016716:PC12 Cells; D010446:Peptide Fragments; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C439320:amyloid beta-protein (25-36); D014810:Vitamin E; D020932:Nerve Growth Factor; D020169:Caspases