Uptake of a neurotoxin-candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine transport system

Abstract

Uptake of catechol isoquinolines to dopamine cells was studied using human dopaminergic neuroblastoma SH-SY5Y cells. Only (R)-1,2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-1,2-DiMeDHTIQ] was transported by dopamine uptake system, while (S)-1,2-DiMeDHTIQ, (R)- and (S)-1-methyl-6,7-dihydroxy-tetrahydroisoquinoline, and 1,2-dimethyl-6,7-dihydroxyisoquinolinum ion were not. Kinetical study showed that the uptake of (R)-1,2-DiMeDHTIQ followed the Michaelis-Menten equation, and the values of the Michaelis constant and the maximal velocity were obtained to be 102.6 +/- 36.9 microM and 66.0 +/- 2.8 pmol/min/mg protein. Dopamine was found to inhibit (R)-1,2-DiMeDHTIQ uptake competitively. These results suggest that the selective uptake by dopamine transporter may account for the specific neurotoxicity of (R)-1,2-DiMeDHTIQ to dopamine neurons.

Valproic acid‐mediated Hsp70 induction and anti‐apoptotic neuroprotection in SH‐SY5Y cells

“…In the present study, we have tested the ability of VPA in neuroprotection against rotenone-induced apoptosis in SH-SY5Y, a human DAergic cell line often used for study of neurodegeneration mechanisms relevant to PD [15][16][17]. By using this rotenone-induced apoptosis cell model, we have evaluated the role of Hsp70 and several critical signaling pathways involved in VPA-mediated neuroprotection.…”

Original article The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson’s disease

“…S1P significantly enhanced cell viability mainly by activation of S1P1 receptor mediated signalling [41]. In our previous and in this study we used human dopaminergic SH-SY5Y cells, because they express tyrosine hydroxylase (HT), dopamine β-hydroxylase (DBH) [38] and the dopamine transporter (DAT) [24,51,59] and have been widely used to gain a better understanding of the molecular processes and pathomechanism of PD. In the present study we investigated gene expression for Sphk1/2 and for enzymes involved in S1P degradation (SPL and SPP).…”

The role of autophagy in neurotoxicity caused by extracellular ASYN

“…Izabrana ćelijska linija pokazuje neke karakteristike dopaminergičkih neurona -mogućnost sinteze dopamina i noradrenalina usled ekspresije dopamin-i tirozin-β-hidroksilaze (16) i ekspresiju transportera dopamina (DAT) na membrani (17). Diferencijacija ćelija do neurona izvršena je "all-trans" retinoičnom kiselinom (engl.…”