Actions of Neurotoxic β-Amyloid on Calcium Homeostasis and Viability of PC12 Cells Are Blocked by Antioxidants but Not by Calcium Channel Antagonists |
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Authors: | Yan Zhou Venkat Gopalakrishnan † J Steven Richardson |
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Institution: | Departments of Pharmacology and; Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada |
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Abstract: | Abstract: The fragment of β-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 β-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 β-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. β-Amyloid 25–35 is also neurotoxic and produces a concentration-dependent reduction in the viability of PC12 cells in culture. The neurotoxic action of β-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 β-amyloid in PC12 cells are mediated by free radical-based processes. |
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Keywords: | Alzheimer's disease β-Amyloid 25–35 Calcium Cytotoxicity Lazaroids Free radicals Antioxidants |
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