NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition: implications for Huntington's disease.

Abstract

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.

• Authors: Maddalena Napolitano, Daniela Zei, Diego Centonze, Rocco Palermo, Giorgio Bernardi, Alessandra Vacca, Paolo Calabresi, Alberto Gulino
• Journal: Neuroscience letters (Neurosci Lett) Vol. 434 Issue 3 Pg. 241-6 (Apr 04 2008) ISSN: 0304-3940 [Print] Ireland
• PMID: 18329171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• NF-kappa B
• Nitro Compounds
• Propionates
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Electron Transport Complex II
• Succinate Dehydrogenase
• 3-nitropropionic acid

Topics

• Active Transport, Cell Nucleus (drug effects, physiology)
• Animals
• Cell Line, Tumor
• Electron Transport Complex II (metabolism)
• Enzyme Inhibitors
• Gene Expression Regulation, Enzymologic (drug effects, physiology)
• Humans
• Huntington Disease (chemically induced, genetics, metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type I (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Nitro Compounds
• Organ Culture Techniques
• Oxidative Stress
• Propionates
• Rats
• Rats, Wistar
• Succinate Dehydrogenase (antagonists & inhibitors, metabolism)
• Transcriptional Activation (drug effects, physiology)