title: Concentration-dependent opposite effects of 1-benzyl-1,2,3,4-tetrahydroisoquinoline on markers of apoptosis: in vitro and ex vivo studies.
abstract: 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was shown to be neurotoxic to the dopaminergic neurons, and thus it was proposed to be an endogenous risk factor leading to Parkinson's disease. In order to better understand the molecular mechanisms of 1BnTIQ-produced toxicity, we examined the impact of different concentrations of 1BnTIQ (50, 100, and 500 μM) on glutamate-induced apoptotic pathway. We measured the markers of apoptosis, such as caspase-3 activity, lactate dehydrogenase release, and mitochondrial membrane potential. Molecular data were supported at the cellular level by calcein AM and Hoechst 33342 staining. The obtained data demonstrated concentration-dependent effects of 1BnTIQ opposing apoptosis, and evidenced that 1BnTIQ in a low concentration (50 μM) exhibited neuroprotective activity, whereas in 10 times higher concentration (500 μM) might be neurotoxic, and significantly intensified glutamate-induced increase in apoptosis markers. Additionally, using an ex vivo molecular study we indicated that both acute and chronic administration of 1BnTIQ did not affect the level of alpha synuclein and tyrosine hydroxylase protein in the rat substantia nigra. Summarizing the studies, we suggest that 1BnTIQ is a rather weak endogenous neurotoxin; however, it should be taken into account that in higher μmoles concentrations, it can initiate apoptosis in the central nervous system and may be involved in the etiopathology of neurodegenerative diseases.
authors.affiliation: Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343, Kraków, Poland, wasik@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kajta
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lenda
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D044005:Tetrahydroisoquinolines; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; C084924:1,2,3,4-tetrahydro-1-(phenylmethyl)isoquinoline