Research on an in vitro cell system for testing the neurotoxicity of kynurenine pathway metabolites.
Quinolinic acid (QUIN), kynurenine acid (KYNA) and 3-hydroxykynurenine (3-HK) - metabolites of the kynurenine pathway are considered to be associated with many central nervous system diseases. However, in neuroscience research in order to test neurotoxicity or neuroprotection against these compounds only primary cell models are available. In this investigation we aimed to develop a simple, rapid and accurate cellular in vitro model using immortalized human neuroblastoma cell lines, namely SK-N-SH and SH-SY5Y differentiated by treatment with various agents. In order to alter the cell response to the neurotoxins, tumor necrosis factor-alpha and retinoic acid (RA) as differentiating agents and modulation of the cellular metabolism through changing the sugar composition from galactose to glucose in media were used. Our results indicated that although RA-differentiation of both cell lines induced the expression of neuronal features, cell vulnerability after exposure to control neurotoxicants (salsolinol, 6-hydroxydopamine) and 3-HK was decreased in comparison to untreated cells and was not influenced after exposure to QUIN and KYNA. Interestingly, the same observations were done in cells grown in galactose containing media.
Institut für Pharmazie/Pharmazeutische Biologie, Freie Universität Berlin, Germany.
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Wszelaki
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Melzig
D001932:Brain Neoplasms / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D005455:Fluorescent Antibody Technique; D006801:Humans; D006892:Hydroxydopamines / Q000633:toxicity; D007546:Isoquinolines / Q000633:toxicity; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014212:Tretinoin / Q000494:pharmacology
D004396:Coloring Agents; D006892:Hydroxydopamines; D007546:Isoquinolines; D009498:Neurotoxins; D013778:Tetrazolium Salts; D013844:Thiazoles; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014212:Tretinoin; C036617:salsolinol; C022616:thiazolyl blue; D017378:Quinolinic Acid