L-type Calcium Channels are Involved in Iron-induced Neurotoxicity in Primary Cultured Ventral Mesencephalon Neurons of Rats
In the present study, we investigated the mechanisms underlying the mediation of iron transport by L-type Ca2+ channels (LTCCs) in primary cultured ventral mesencephalon (VM) neurons from rats. We found that co-treatment with 100 µmol/L FeSO4 and MPP+ (1-methyl-4-phenylpyridinium) significantly increased the production of intracellular reactive oxygen species, decreased the mitochondrial transmembrane potential and increased the caspase-3 activation compared to MPP+ treatment alone. Co-treatment with 500 µmol/L CaCl2 further aggravated the FeSO4-induced neurotoxicity in MPP+-treated VM neurons. Co-treatment with 10 µmol/L isradipine, an LTCC blocker, alleviated the neurotoxicity induced by co-application of FeSO4 and FeSO4/CaCl2. Further studies indicated that MPP+ treatment accelerated the iron influx into VM neurons. In addition, FeSO4 treatment significantly increased the intracellular Ca2+ concentration. These effects were blocked by isradipine. These results suggest that elevated extracellular Ca2+ aggravates iron-induced neurotoxicity. LTCCs mediate iron transport in dopaminergic neurons and this, in turn, results in elevated intracellular Ca2+ and further aggravates iron-induced neurotoxicity.
KeywordsL-type Ca2+ channels Iron overload Parkinson’s disease Isradipine Dopamine neuron
This work was supported by grants from the National Natural Science Foundation of China (81671249) and the Natural Science Foundation of Shandong Province, China (ZR2016CM04).
Conflict of interest
The authors declare that they have no conflict of interest.
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