Modulation of neurotoxicant-induced increases in intracellular calcium by phytoestrogens differ for amyloid beta peptide (Abeta) and 1-methyl-4-phenyl-pyridine (MPP(+)).
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.
Sørensen
Izel Fourie
IF
Department of Animal Health, Welfare and Nutrition, Faculty of Agricultural Sciences, University of Aarhus, Denmark.
Purup
Stig
S
Ehrich
Marion
M
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*
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