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 delta (PKC delta) shows the ability to regulate the activity of the Nox system. Herein we aimed to investigate if also in dopaminergic neurons exposed to PQ, PKC delta can regulate Nox1 expression. The chemical inhibitor, rottlerin, and short interference RNA (siRNA) were used to inhibit or selectively knockdown PKC delta, 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 PKC delta-siRNA. We observed that inhibition or knockdown of PKC delta significantly reduced PQ induced Nox1 transcript and protein levels, ROS generation and subsequent dopaminergic cell death. The results suggest that PKC delta 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. (C) 2013 Elsevier Inc. All rights reserved.