TY - JOUR
T1 - NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition
T2 - Implications for Huntington's disease
AU - Napolitano, Maddalena
AU - Zei, Daniela
AU - Centonze, Diego
AU - Palermo, Rocco
AU - Bernardi, Giorgio
AU - Vacca, Alessandra
AU - Calabresi, Paolo
AU - Gulino, Alberto
PY - 2008/4/4
Y1 - 2008/4/4
N2 - Nuclear factor-kB (NF-kB) is a family of DNA-binding proteins that are important regulators involved in immune and inflammatory responses, as well as in cell survival and apoptosis. In the nervous system NF-kB is activated under physiological and pathological conditions including learning and memory mechanisms and neurodegenerative diseases. NF-kB is activated in neurons in response to excitotoxic, metabolic and oxidative stress and there is a body of evidence to suggest that glutamate induces NF-kB by the main ionotropic glutamate receptors. In the present study, 3 nitroproprionic acid (3NP), an irreversible inhibitor of succinate dehydrogenase (SD, complex II) has been employed to provide an experimental model of Huntington's disease (HD). Specifically, we described 3NP-induced activation of NF-kB and of iNOS and nNOS genes in striatal treated slices. To aim to better understand the relationship between these identified dysregulated genes and mitochondrial dysfunction, we investigated in SK-N-MC human neuroblastoma cells following 3NP treatment, whether NF-kB nuclear translocation and activation might be involved in the mechanisms by which 3NP leads to transcriptional activation of NOS genes. These results are relevant to more precisely define the role of NF-kB in neuronal cells and better understand its putative involvement in neurodegeneration.
AB - Nuclear factor-kB (NF-kB) is a family of DNA-binding proteins that are important regulators involved in immune and inflammatory responses, as well as in cell survival and apoptosis. In the nervous system NF-kB is activated under physiological and pathological conditions including learning and memory mechanisms and neurodegenerative diseases. NF-kB is activated in neurons in response to excitotoxic, metabolic and oxidative stress and there is a body of evidence to suggest that glutamate induces NF-kB by the main ionotropic glutamate receptors. In the present study, 3 nitroproprionic acid (3NP), an irreversible inhibitor of succinate dehydrogenase (SD, complex II) has been employed to provide an experimental model of Huntington's disease (HD). Specifically, we described 3NP-induced activation of NF-kB and of iNOS and nNOS genes in striatal treated slices. To aim to better understand the relationship between these identified dysregulated genes and mitochondrial dysfunction, we investigated in SK-N-MC human neuroblastoma cells following 3NP treatment, whether NF-kB nuclear translocation and activation might be involved in the mechanisms by which 3NP leads to transcriptional activation of NOS genes. These results are relevant to more precisely define the role of NF-kB in neuronal cells and better understand its putative involvement in neurodegeneration.
KW - 3-nitropropionic acid
KW - Basal ganglia
KW - Huntington's disease
KW - NF-kB
KW - NOS
UR - http://www.scopus.com/inward/record.url?scp=40849123838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40849123838&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2007.09.056
DO - 10.1016/j.neulet.2007.09.056
M3 - Article
C2 - 18329171
AN - SCOPUS:40849123838
VL - 434
SP - 241
EP - 246
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -