TY - JOUR
T1 - PKCδ mediates paraquat-induced Nox1 expression in dopaminergic neurons
AU - Cristóvão, Ana Clara
AU - Barata, Joana
AU - Je, Goun
AU - Kim, Yoon Seong
N1 - Funding Information:
Ana Clara Cristóvão supported by the Portuguese Foundation for Science and Technology – FCT ( SFRH/BPD/69643/2010 ).
Funding Information:
This work was supported by the US National Institute of Health [ Grant number: RO1 NS062827 to Y.S.K.] and Michael J. Fox Foundation [ Grant number: Target Validation 2009 to Y.S.K.].
PY - 2013/8/2
Y1 - 2013/8/2
N2 - 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.
AB - 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.
KW - NADPH oxidase
KW - Paraquat
KW - Parkinson Disease
KW - Protein Kinase C delta
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U2 - 10.1016/j.bbrc.2013.06.085
DO - 10.1016/j.bbrc.2013.06.085
M3 - Article
C2 - 23827392
AN - SCOPUS:84880964990
SN - 0006-291X
VL - 437
SP - 380
EP - 385
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -