Browsing by Author "Barata, Joana Ribeiro"
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- The role of PKCd [delta] as a regulator of the Nox1 contribution for the mechanism of paraquat induced dopaminergic neurotoxicityPublication . Barata, Joana Ribeiro; Baltazar, Graça Maria Fernandes; Cristóvão, Ana ClaraParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc), to which contribute the combination of aging and genetic and environmental factors. Several studies clearly showed an increase in the incidence of PD in rural environments, and hypothesized the involvement of pesticides, like paraquat (PQ), in the mechanisms of neurodegeneration. PQ can be reduced by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzyme and can induce its toxicity through the production of superoxide anions, which leads to the accumulation of reactive oxygen species (ROS) in the cell. Matsuzaki and its collaborators showed that ROS formation induced by PQ facilitate α-synuclein association, a biochemical hallmark of PD. The Nox system generates ROS in a regulated manner, producing ROS in various tissues. It has been suggested that Nox1 subunit plays a role in plays a role in the oxidative stress and subsequent DA cell death elicited by PQ. Protein kinase C delta (PKCδ) has been showed to be involved in apoptotic signaling pathways, by phosphorylation and activation of several inducers of cell death. PQ induces an increase of ROS production and death of DA neurons. In the present work we aimed to investigate in PQ exposed cells the possible relationship between ROS generation by Nox1 and the putative regulatory effect of PKCδ in the process. To investigate whether PKCδ influences ROS production, DA cell death and Nox1 expression, short interference RNA (siRNA) was used to specifically knockdown PKCδ. Transfection with PKCδ-siRNA decrease mRNA levels by 32% and protein levels by 54%. We observed that ROS and DA cell death induced by PQ were significantly reduced by PKCδ knockdown, in N27 cells transfected with PKCδ-siRNA. This study also revealed that, in DA neurons, the upregulation of Nox1 mRNA and protein induced by PQ exposure is reversed when PKCδ is knockdown, suggesting a possible involvement of PKCδ in the regulation of Nox1 expression pathways affected by PQ.