Role of nuclear factor‐kappa B in mitochondria‐derived superoxide‐lowered protein expression of voltage‐gated sodium channels in nodose neurons from heart failure rats

Abstract

Our previous study has shown that chronic heart failure (CHF) reduces protein expression of voltage‐gated sodium (Nav) channels in rat nodose neurons. In the present study, we investigated the involvements of mitochondrial superoxide and nuclear factor‐kappa B (NF‐kB) in CHF‐decreased Nav channel expression in rat nodose neurons. CHF was induced by left coronary ligation. CHF reduced the protein expression of manganese superoxide dismutase (MnSOD) and elevated mitochondrial superoxide level in the nodose neurons. Adenoviral MnSOD (Ad.MnSOD) gene transfection (50 multiplicity of infection) into the nodose neurons normalized the MnSOD expression, reduced the elevation of mitochondrial superoxide, and partially reversed the reduced protein expression of Nav channels in the CHF nodose neurons. Additionally, protein expression of NF‐kB p65 and phosphorylated NF‐kB p65 in the nodose neurons was higher in CHF rats than that in sham rats. Treatment with an NF‐kB inhibitor (caffeic acid phenethyl ester, 10 ìM, 24 h) significantly increased Nav channel density in CHF nodose neurons. Furthermore, Ad.MnSOD inhibited the NF‐kB p65 binding to Nav channel promoter in CHF nodose neurons. These results indicate that mitochondrial superoxide lowered protein expression of Nav channels in CHF nodose neurons via activating NF‐kB.