title: PKCδ mediates paraquat-induced Nox1 expression in dopaminergic neurons.
abstract: Our previous works have shown that the (NADPH) oxidase (Nox) enzyme, in particular Nox1, plays an important role in oxidative stress and subsequent dopaminergic cell death elicited by paraquat (PQ). In non-neuronal and glial cells, protein kinase C δ (PKCδ) shows the ability to regulate the activity of the Nox system. Herein we aimed to investigate if also in dopaminergic neurons exposed to PQ, PKCδ can regulate Nox1 expression. The chemical inhibitor, rottlerin, and short interference RNA (siRNA) were used to inhibit or selectively knockdown PKCδ, respectively. The studies were performed using the immortalized rat mesencephalic dopaminergic cell line (N27 cells) exposed to PQ, after pre-incubation with rottlerin or transfected with PKCδ-siRNA. We observed that inhibition or knockdown of PKCδ significantly reduced PQ induced Nox1 transcript and protein levels, ROS generation and subsequent dopaminergic cell death. The results suggest that PKCδ plays a role in the regulation of Nox1-mediated oxidative stress elicited by PQ and could have a role in the pathogenesis of Parkinson's disease.
authors.affiliation: University of Central Florida, Burnett School of Biomedical Sciences, College of Medicine, Orlando, Fl, USA. aclara@fcsaude.ubi.pt
authors.forename: Ana Clara
authors.initials: AC
authors.lastname: Cristóvão
authors.forename: Joana
authors.initials: J
authors.lastname: Barata
authors.forename: Goun
authors.initials: G
authors.lastname: Je
authors.forename: Yoon-Seong
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D004298:Dopamine / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000074624:NADPH Oxidase 1; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010269:Paraquat / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D017382:Reactive Oxygen Species; C085746:rottlerin; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat; D051745:Protein Kinase C-delta; D010269:Paraquat; D004298:Dopamine
keywords: NADPH oxidase; Paraquat; Parkinson Disease; Protein Kinase C delta