Modulation of neurotoxicant‐induced increases in intracellular calcium by phytoestrogens differ for amyloid beta peptide (Aβ) 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.

Calcium Signaling in Neuronal Cells Exposed to the Munitions Compound Cyclotrimethylenetrinitramine (RDX)

“…The procedure was similar to that used previously in our laboratory. 20 For experiments in which mechanisms associated with increases in calcium were examined, RDX in concentrations sufficient to produce relatively high consistent and immediate peaks of calcium influx (7.5 and 1.5 mM) were used. For these experiments, human SH-SY5Y cells (4 × 10 4 cells/well, 200 μL) were grown overnight in 96-well plates prior to cellular Ca 2+ measurements.…”

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia

“…They showed that glycitein interacted with Aβ monomers, oligomers, and fibrils, and the effect of equol was much weaker than glycitein. Using SH-SY5Y neuroblastoma cells cultured with amyloid-β and 1-methyl-4-phenyl-pyridine, Sorensen et al investigated the effect of equol and genistein on the neurotoxicant-induced elevation of intracellular calcium [ 116 ]. The neurotoxicants caused an increase in Ca 2+ and both equol and genistein attenuated the increase in Ca 2+ .…”