Comparative characteristic of thiamine antagonists on apoptosis induction in different types of nerve cell lines.
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.
Chornyy
S A
SA
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv. sch_1982@yahoo.com
Parkhomenko
Yu M
YM
D000670:Amprolium / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010119:Oxythiamine / Q000494:pharmacology; D016716:PC12 Cells; D011745:Pyrithiamine / Q000494:pharmacology; D051381:Rats; D013831:Thiamine / Q000037:antagonists & inhibitors*; D013832:Thiamine Deficiency / Q000150:complications / Q000378:metabolism; D013997:Time Factors
D010119:Oxythiamine; D011745:Pyrithiamine; D000670:Amprolium; D013831:Thiamine