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6-Hydroxydopamine Upregulates Iron Regulatory Protein 1 by Activating Certain Protein Kinase C Isoforms in the Dopaminergic MES23.5 Cell Line

6-Hydroxydopamine Upregulates Iron Regulatory Protein 1 by Activating Certain Protein Kinase C Isoforms in the Dopaminergic MES23.5 Cell Line

Wenjie Wang, Ning Song, Haoyun Zhang, Junxia Xie, Jun Wang

Int J Biochem Cell Biol. 2012 Nov;44(11):1987-92.

PMID: 22846799

Abstract:

Iron-induced oxidative stress is thought to play a crucial role in the pathogenesis of Parkinson's disease. Our previous studies demonstrated that decreased expression of ferroportin 1 contributes to 6-hydroxydopamine induced intracellular iron accumulation and that decreased ferroportin 1 expression is caused by increased expression of iron regulatory protein 1. Iron regulatory protein 1 is a central regulator of iron homeostasis and is a likely target of extracellular agents to program changes in cellular iron metabolism. Therefore, the mechanism of iron regulatory protein 1 upregulation induced by 6-hydroxydopamine has become a significant focus of research. Iron regulatory protein 1 is regulated by protein kinase C, although this regulation is tissue specific. Therefore, in the present study, we aimed to determine whether alteration of protein kinase C activity modified iron regulatory protein 1 expression in the dopaminergic MES23.5 cell line, Furthermore, we investigated whether 6-hydroxydopamine induced iron regulatory protein 1 upregulation is mediated by protein kinase C, thus achieving regulation of cellular iron levels. The results showed that iron regulatory protein 1 was upregulated by phorbol 12-myristate-13-acetate, the PKC activator in dopaminergic MES23.5 cells, and ferroportin 1 expression and iron efflux were decreased as a result of iron regulatory protein 1 upregulation. The protein kinase C inhibitor bisindolylmaleimide I hydrochloride abolished the effect of phorbol 12-myristate-13-acetate. Protein kinase C-δ and protein kinase C-ζ, but not protein kinase C-ɛ were activated by 6-hydroxydopamine. The protein kinase C-δ inhibitor rottlerin inhibited protein kinase C-δ phosphorylation and abolished iron regulatory protein 1 upregulation induced by 6-hydroxydopamine. The protein kinase C-ζ pseudo-substrate inhibitor inhibited protein kinase C-ζ phosphorylation and abolished iron regulatory protein 1 upregulation induced by 6-hydroxydopamine. These data indicate that iron regulatory protein 1 is regulated by protein kinase C in dopaminergic MES23.5 cells and that protein kinase C activated by 6-hydroxydopamine regulates iron regulatory protein 1 expression, thus achieving regulation of cellular iron levels.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP176504362-B	GF 109203X hydrochloride		176504-36-2	Price

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