粒線體與神經細胞死亡的研究(2/2)
Date Issued
2004
Date
2004
Author(s)
李旺祚
DOI
922314B002102
Abstract
3-Nitropropionic acid (3-NP) is an
irreversible inhibitor of succinate dehydrogenase.
Previous studies had shown that 3-NP can lead to
neuronal death following the activation of
caspases. In the present study, we first
investigate the neurotoxicity of
methamphetamine and amphetamine in primary
rat cortical neuronal cultures, and will compare
the pathogenic mechanisms of neuronal death in
methamphetamine and amphetamine with those
in 3-NP. We found that there was a dose- and
time-dependent increase of neuronal death
following the application of methamphetamine
and amphetamine. Significant elevation of
reactive oxygen species was also found after the
application of the drugs, especially in
methamphetamine. Addition of low
concentration of 3-NP significantly decreased the
cellular ATP in amphetamine-treated neurons,
indicating the effect of the drug on mitochondrial
function. However, compared with that in 3-NP
neurotoxicity, only mild activation of caspase-3
was found following the treatment of
amphetamine. We further found that the
caspase-3 activation in amphetamine and
methamphetamine developed following
mitochondrial depolarization. On the contrary,
the caspase-3 activation in 3-NP developed
before mitochondrial depolarization, indicating
both a mitochondrial-dependent and independent
pathways in 3-NP neurotoxicity. Because 3-NP is
a direct mitochondrial toxins while amphetamine
and methamphetamine are both indirect
mitochondrial toxins, whether that’s one of the
reasons leading to different caspase-3 activation
needs further investigation.
Subjects
3-nitropropionic acid
amphetamine
methamphetamine
caspase
apoptosis
mitochondria
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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