Comparative characteristic of thiamine antagonists on apoptosis induction in different types of nerve cell lines
S A Chornyy1, Yu M Parkhomenko
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv. sch_1982@yahoo.com
Abstract:
Abnormalities in oxidative metabolism and inflammation accompany many neurodegenerative diseases. The mechanisms of neurodegeneration induced by thiamine deficiency remain incompletely elucidated. The susceptibility of various types of nerve cells to thiamine (vitamin B) antagonists--oxythiamine (OT), pyrithiamine (PT) and amprolium (Am) was investigated. Four cell lines (neuronally differentiated rat PC-12, rat astrocytes DITNC, neuronally differentiated human SH-SY5Y and human astrocytic cells 1321N1) were used for experiments as neural cell models. When different cell types were cultivated with thiamine antagonists, a significant decrease of viability was detected in a time- and dose-dependent manner as demonstrated by the WST-1 colorimetric assay. These data were similar to those of caspase 3 activity and DNA fragmentation induced by thiamine antagonists. All tested cell lines were more vulnerable to OT and PT than to Am. Am displayed a pronounced damaging action on neuronal cells and had a modest influence on astrocytes. The last observation gives the basis to suppose, that neuronal cells need external arrival of thiamine more than astrocytes. Thus, the results testify that various types of nerve cells have different susceptibility to the thiamine antagonists and this relates to extent of apoptosis development.
Insights
Thiamine antagonists like oxythiamine and pyrithiamine induce neurodegeneration by increasing apoptosis. Neuronal cells show higher susceptibility to these thiamine (vitamin B) antagonists than astrocytes.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neurodegenerative diseases are linked to oxidative metabolism and inflammation.
- Mechanisms of neurodegeneration from thiamine deficiency are not fully understood.
Purpose of the Study:
- Investigate the susceptibility of different neural cell types to thiamine antagonists.
- Determine the impact of oxythiamine, pyrithiamine, and amprolium on neural cell viability and apoptosis.
Main Methods:
- Utilized four neural cell lines: rat PC-12, rat astrocytes DITNC, human SH-SY5Y, and human astrocytic cells 1321N1.
- Assessed cell viability using the WST-1 assay.
- Measured caspase 3 activity and DNA fragmentation to evaluate apoptosis.
Main Results:
- Thiamine antagonists decreased cell viability in a time- and dose-dependent manner across all cell lines.
- Oxythiamine and pyrithiamine were more toxic than amprolium.
- Amprolium primarily damaged neuronal cells, with less impact on astrocytes, suggesting higher thiamine dependency in neurons.
Conclusions:
- Neural cell types exhibit varying susceptibility to thiamine antagonists.
- Thiamine deficiency-induced neurotoxicity involves apoptosis, with neurons being more vulnerable than astrocytes.
