Resistance of the insect cell line IPLB-LdFB to salsolinol-induced apoptosis.
Apoptosis is a form of cell death that is manifested in Parkinson's disease (PD) and certain other neurodegenerative disorders. Metabolites of salsolinol (SAL), an intraneuronal, dopamine-derived tetrahydroisoquinoline (TIQ), have been shown to induce apoptosis in human dopaminergic neuroblastoma cells, implicating these molecules as causative or contributory factors in the selective killing of nigrostriatal dopaminergic neurons, a cardinal manifestation of Parkinson's disease. Since insects employ dopamine and related catecholamines in a variety of processes including cuticular sclerotization and cellular immune reactions, it was of interest to know how insect cells metabolized exogenous SAL. Propidium iodide staining combined with flow cytometry showed that IPLB-LdFB cells from Lymantria dispar exhibited no significant (P < 0.05) increase in apoptosis when incubated for 48 h with concentrations of SAL ranging from 10 microM to 1 mM. A significant increase in apoptosis (P < 0.05) was observed in cell cultures containing the highest concentration of SAL tested (5 mM), but only 12.4% of the cells manifested this form of cell death. High pressure liquid chromatography with electrochemical detection (HPLC-ED) was used to document the production of two potentially cytotoxic quinonoids generated during the autoxidation of SAL, a reaction that was found to be significantly (P < 0.05) enhanced by peroxidase. The resistance of IPLB-LdFB cells to SAL-induced apoptosis is attributed to the ability of these insect cells to metabolize and/or detoxify such dopamine-derived catecholic TIQs. Thus, the biochemical pathways employed by insect cells in these processes may be of considerable interest to individuals investigating certain neurodegenerative disorders.
Ottaviani
Enzo
E
Department of Animal Biology, University of Modena and Reggio Emilia, Modena, Italy. ottaviani.enzo@unimo.it
Nappi
Anthony J
AJ
Vass
Emily
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D007915:Lepidoptera / Q000166:cytology* / Q000378:metabolism
D007546:Isoquinolines; C036617:salsolinol