title: Modulation of neurotoxicant-induced increases in intracellular calcium by phytoestrogens differ for amyloid beta peptide (Abeta) and 1-methyl-4-phenyl-pyridine (MPP(+)).
abstract: Neurotoxicant-induced elevation of intracellular calcium (Ca(2+)) and modulation by phystoestrogens were examined in vitro using human neuroblastoma SH-SY5Y cells cultured with amyloid beta-peptide (Abeta) and 1-methyl-4-phenyl-pyridine (MPP+). Although Abeta itself did not increase Ca(2+), it exacerbated the effects of carbachol. The elevation of Ca(2+) caused by the agents in combination could be reduced by pretreatment with the phytoestrogens equol and genistein, as well as by the L-type Ca(2+) channel blocker nifedipine. MPP+ exposure also elevated Ca(2+), an effect blocked by nifedipine but not by the phytoestrogens. As opposed to phytoestrogens, nifedipine was also able to significantly reduce cell death caused by higher concentrations of MPP(+) in the LDH viability assay. The results suggest that phytoestrogens are unlikely to serve as general cellular protectants for neurotoxicants with different mechanisms of action. The concentrations of Abeta and MPP(+) affecting Ca(2+) release did not inhibit cell viability as measured with the LDH release assay. This indicates that mechanisms involved with toxicity can be studied at doses that are not lethal.
authors.affiliation: Department of Animal Health, Welfare and Nutrition, Faculty of Agricultural Sciences, University of Aarhus, Denmark.
authors.forename: Izel Fourie
authors.initials: IF
authors.lastname: Sørensen
authors.forename: Stig
authors.initials: S
authors.lastname: Purup
authors.forename: Marion
authors.initials: M
authors.lastname: Ehrich
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004336:Drug Antagonism; D060754:Equol; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology*
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D016229:Amyloid beta-Peptides; D007529:Isoflavones; D009498:Neurotoxins; D048789:Phytoestrogens; D060754:Equol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019833:Genistein; D007770:L-Lactate Dehydrogenase; D009543:Nifedipine; D002118:Calcium