Involvement of nuclear factor‐kappa B in superoxide‐lowered protein expression of voltage‐gated sodium channels in nodose ganglia from heart failure rats

Abstract

Our previous study has shown that chronic heart failure (CHF) elevates mitochondria‐derived superoxide level and reduces protein expression of voltage‐gated sodium (Nav) 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 Nav1.7 channel expression in rat nodose ganglia. CHF was induced by left coronary ligation. Adenoviral MnSOD (Ad.MnSOD) gene (4 × 1010 PFU/ml, 1 μl) or lentiviral NF‐kB (p65) shRNA (5 × 106 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 Nav1.7 expression were measured by western blot. NF‐κB binding to the promoter of Nav1.7 channels was detected with chromosome immunoprecipitation assay (ChIP). We found that: 1) HF decreased Nav1.7 expression, increased NF‐kB (p65) phosphorylation and NF‐kB (p65) binding with Nav1.7 promoter; 2) NF‐kB (p65) shRNA reduced total and phosphorylated NF‐kB (p65) and increased Nav1.7 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 Nav1.7 expression in the nodose ganglia from CHF rat. These results indicate that mitochondrial superoxide overproduction triggered NF‐kB activation and subsequently depressed Nav1.7 expression in CHF nodose neurons.