Cytotoxicity of endogenous isoquinolines to human dopaminergic neuroblastoma SH-SY5Y cells

Abstract

Endogenous isoquinolines with and without catechol structure have been proposed to be neurotoxins specific for dopamine neurons. In this paper they were examined for the cytotoxicity of human dopaminergic neuroblastoma SH-SY5Y cells. The cytotoxicity was quantitatively determined using Alamar Blue assay, by which the reduction-oxidation potency in the living cells can be measured spectrometrically. 1,2-Dimethyl-6,7-dihydroxyisoquinolinium ion [1,2-DMDHIQ+], an oxidation product of a parkinsonism-inducing isoquinoline, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahroisoquinoline [N-methyl-(R)salsolinol, NM(R)Sal] was found to be the most potent toxin among isoquinolines examined. In general, catechol isoquinolines were more toxic than isoquinolines without catechol structure. With and without catechol structure, the oxidized isoquinolinium ion having methyl groups at C-1 and N-2 positions proved to be more cytotoxic than the simple isoquinolines. The involvement of 1,2-DMDHIQ+ to the neurotoxicity of NM(R)Sal was suggested and discussed.