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Oxidant treatment causes a dose‐dependent phenotype of apoptosis in cultured motoneurons
Author(s) -
Kaal Evert C.A.,
Veldman Henk,
Sodaar Peter,
Joosten Elbert A.J.,
Dop Bär P.R.
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19981215)54:6<778::aid-jnr5>3.0.co;2-0
Subject(s) - reactive oxygen species , catalase , apoptosis , programmed cell death , hydrogen peroxide , oxidative stress , sod1 , chemistry , superoxide dismutase , toxicity , antioxidant , superoxide , neurotoxin , pharmacology , biochemistry , biology , enzyme , organic chemistry
Evidence is growing that reactive oxygen species (ROS), by‐products of (normal) cellular aerobic metabolism, are involved in the pathogenesis of neurodegenerative diseases. One of these diseases is amyotrophic lateral sclerosis (ALS), in which motoneurons die, leading to paralysis and death. It remains uncertain whether ROS are the cause of (apoptotic) motoneuron death in ALS. To further understand the role of ROS in motoneuron death, we investigated the effects of ROS on isolated spinal rat motoneurons in culture. ROS were generated with a combination of iron(III) and ascorbate, or with hydrogen peroxide. Both toxic treatments resulted in a dose‐dependent motoneuron death. Iron(III)/ascorbate toxicity was completely prevented with the hydrogen peroxide detoxifying enzyme catalase and partially prevented with the antioxidant vitamin E. SOD1, the enzyme that removes superoxide, did not protect against iron(III)/ascorbate toxicity. ROS treatment caused apoptotic motoneuron death: low doses of iron(III)/ascorbate or hydrogen peroxide resulted in complete apoptosis ending in nuclear fragmentation, while high doses of ROS resulted in incomplete apoptosis (nuclear condensation). Thus, depending on the dose of ROS, the motoneurons complete the apoptotic pathway (low dose) or are stopped somewhere during this route (high dose). J. Neurosci. Res. 54:778–786, 1998. © 1998 Wiley‐Liss, Inc.