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Actions of Neurotoxic β‐Amyloid on Calcium Homeostasis and Viability of PC12 Cells Are Blocked by Antioxidants but Not by Calcium Channel Antagonists
Author(s) -
Zhou Yan,
Gopalakrishnan Venkat,
Richardson J. Steven
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67041419.x
Subject(s) - calcium , calcium channel , homeostasis , chemistry , calcium metabolism , amyloid (mycology) , pharmacology , neuroscience , biochemistry , biology , microbiology and biotechnology , organic chemistry , inorganic chemistry
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.