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Involvement of nuclear factor‐kappa B in superoxide‐lowered protein expression of voltage‐gated sodium channels in nodose ganglia from heart failure rats
Author(s) -
Tu Huiyin,
Liu Jinxu,
Zhang Dongze,
Muelleman Robert,
Li Yulong
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.699.2
Subject(s) - superoxide , microbiology and biotechnology , small hairpin rna , western blot , chemistry , mitochondrion , downregulation and upregulation , phosphorylation , biology , biochemistry , gene , rna , enzyme
Our previous study has shown that chronic heart failure (CHF) elevates mitochondria‐derived superoxide level and reduces protein expression of voltage‐gated sodium (Na v ) channels in rat nodose neurons. In the present study, we investigated the involvement of mitochondrial superoxide and nuclear factor‐kappa B (NF‐kB) in CHF‐decreased Na v 1.7 channel expression in rat nodose ganglia. CHF was induced by left coronary ligation. Adenoviral MnSOD (Ad.MnSOD) gene (4 × 10 10 PFU/ml, 1 μl) or lentiviral NF‐kB (p65) shRNA (5 × 10 6 IFU/ml, 1 μl) was injected into the nodose ganglia. Mitochondrial superoxide was detected using mitochondria‐targeted superoxide sensitive flurogenic probe MitoSOX. MnSOD, NF‐kB (p65) and Na v 1.7 expression were measured by western blot. NF‐κB binding to the promoter of Na v 1.7 channels was detected with chromosome immunoprecipitation assay (ChIP). We found that: 1) HF decreased Na v 1.7 expression, increased NF‐kB (p65) phosphorylation and NF‐kB (p65) binding with Na v 1.7 promoter; 2) NF‐kB (p65) shRNA reduced total and phosphorylated NF‐kB (p65) and increased Na v 1.7 expression in CHF nodese neurons; 3) Ad.MnSOD transfection elevated MnSOD protein, reduced the elevation of mitochondrial superoxide level and phosphorylated NF‐kB (p65), and increased Na v 1.7 expression in the nodose ganglia from CHF rat. These results indicate that mitochondrial superoxide overproduction triggered NF‐kB activation and subsequently depressed Na v 1.7 expression in CHF nodose neurons.