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Oxidant Injury in PC12 Cells—A Possible Model of Calcium “Dysregulation” in Aging: II. Interactions with Membrane Lipids
Author(s) -
Denisova Natalia A.,
Strain Joy G.,
Joseph James A.
Publication year - 1997
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.1471-4159.1997.69031259.x
Subject(s) - sphingomyelin , oxidative stress , chemistry , calcium , membrane , biophysics , intracellular , membrane potential , calcium in biology , oxidative phosphorylation , cholesterol , endocrinology , medicine , biochemistry , microbiology and biotechnology , biology , organic chemistry
In a model recently developed to study the parameters altering vulnerability to oxidative stress, it was shown via image analysis that H 2 O 2 ‐exposed PC12 cells exhibited increased levels of intracellular Ca 2+ (baseline), decreases in K + ‐stimulated Ca 2+ levels (peak), and decreased poststimulation Ca 2+ clearance (recovery). The present experiments were performed to determine if the response patterns in these parameters to oxidative stress would be altered after modification of membrane lipid composition induced by incubating the PC12 cells with 660 µ M cholesterol (CHL) in the presence or absence of 500 µ M sphingomyelin (SPH) before low (5 µ M ) or high (300 µ M ) H 2 O 2 exposure. Neither CHL nor SPH had synergistic effects with high concentrations of H 2 O 2 on baseline. However, CHL in the presence or absence of SPH reversed the effect of low concentrations of H 2 O 2 on baseline. SPH decreased significantly the cell's ability to clear excess Ca 2+ in the presence or absence of H 2 O 2 and increased significantly the level of conjugated dienes (CDs). It is surprising that in the cells pretreated with CHL, the CD levels were not significantly different from controls. However, in the presence of SPH, the effects of CHL on CDs were altered. These results suggest that the ratios of membrane lipids could be of critical importance in determining the vulnerability to oxidative stress and Ca 2+ translocation in membranes. This may be of critical importance in aging where there is increased membrane SPH and significant loss of calcium homeostasis.