Actions of neurotoxic beta-amyloid on calcium homeostasis and viability of PC12 cells are blocked by antioxidants but not by calcium channel antagonists.
The fragment of beta-amyloid comprised of amino acids 25-35 induces a rapid, concentration-dependent increase in cytosolic free calcium levels in suspensions of PC12 neuronal cells. This action of beta-amyloid 25-35 is not altered by pretreatment with the calcium channel blockers nifedipine or cobalt, with the depleter of intracellular calcium stores cyclopiazonic acid, or with the phospholipase C inhibitor neomycin. However, the effects of beta-amyloid 25-35 on cytosolic free calcium are absent in calcium-free buffer and are blocked by the antioxidant lazaroid U-83836E and by vitamin E. beta-Amyloid 25-35 is also neurotoxic and produces a concentration-dependent reduction in the viability of PC12 cells in culture. The neurotoxic action of beta-amyloid is blocked by U-83836E and vitamin E but not by nifedipine or cobalt. These data indicate that both the disruption of calcium homeostasis and the reduction of cell viability produced by beta-amyloid in PC12 cells are mediated by free radical-based processes.
Zhou
Y
Y
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Gopalakrishnan
V
V
Richardson
J S
JS
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D009355:Neomycin / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014810:Vitamin E / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002121:Calcium Channel Blockers; D002839:Chromans; D004791:Enzyme Inhibitors; D007211:Indoles; D009498:Neurotoxins; D010446:Peptide Fragments; D010879:Piperazines; C074636:amyloid beta-protein (25-35); C066382:U 78517F; D014810:Vitamin E; D003035:Cobalt; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D009355:Neomycin; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid