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4‐Hydroxynonenal Induces Oxidative Stress and Death of Cultured Spinal Cord Neurons
Author(s) -
Malecki Andrzej,
Garrido Rosario,
Mattson Mark P.,
Hennig Bernhard,
Toborek Michal
Publication year - 2000
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.1471-4159.2000.0742278.x
Subject(s) - spinal cord , oxidative stress , arachidonic acid , lipid peroxidation , 4 hydroxynonenal , chemistry , intracellular , neuroprotection , calcium in biology , viability assay , spinal cord injury , programmed cell death , biochemistry , pharmacology , cell , biology , apoptosis , neuroscience , enzyme
Primary spinal cord trauma can trigger a cascade of secondary processes leading to delayed and amplified injury to spinal cord neurons. Release of fatty acids, in particular arachidonic acid, from cell membranes is believed to contribute significantly to these events. Mechanisms of fatty acid‐induced injury to spinal cord neurons may include lipid peroxidation. One of the major biologically active products of arachidonic acid peroxidation is 4‐hydroxynonenal (HNE). The levels of HNE‐protein conjugates in cultured spinal cord neurons increased in a dose‐dependent manner after a 24‐h exposure to arachidonic acid. To study cellular effects of HNE, spinal cord neurons were treated with different doses of HNE, and cellular oxidative stress, intracellular calcium, and cell viability were determined. A 3‐h exposure to 10 μ M HNE caused ∼80% increase in oxidative stress and 30% elevation of intracellular calcium. Exposure of spinal cord neurons to HNE caused a dramatic loss of cellular viability, indicated by a dose‐dependent decrease in MTS [3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2 H ‐tetrazolium, inner salt] conversion. The cytotoxic effect of HNE was diminished by pretreating neurons with ebselen or N ‐acetylcysteine. These data support the hypothesis that formation of HNE may be responsible, at least in part, for the cytotoxic effects of membrane‐released arachidonic acid to spinal cord neurons.