Wenjie Wang, Ning Song, Haoyun Zhang, Junxia Xie, Jun Wang
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Physiology, Medical College of Qingdao University, Qingdao 266071, China.
The international journal of biochemistry & cell biology 2012 NovIron-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. Copyright © 2012 Elsevier Ltd. All rights reserved.
Wenjie Wang, Ning Song, Haoyun Zhang, Junxia Xie, Jun Wang. 6-Hydroxydopamine upregulates iron regulatory protein 1 by activating certain protein kinase C isoforms in the dopaminergic MES23.5 cell line. The international journal of biochemistry & cell biology. 2012 Nov;44(11):1987-92
PMID: 22846799
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