Modulation of neurotoxicant-induced increases in intracellular calcium by phytoestrogens differ for amyloid beta peptide (Aβ) and 1-methyl-4-phenyl-pyridine (MPP+)

✍ Scribed by Izel Fourie Sørensen; Stig Purup; Marion Ehrich

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 194 KB
• Volume: 29
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1376

✦ Synopsis

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 (A__β__) and 1‐methyl‐4‐phenyl‐pyridine (MPP+). Although A__β__ 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 A__β__ 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. Copyright © 2008 John Wiley & Sons, Ltd.