Activation of Wnt/β-catenin signaling by hydrogen peroxide transcriptionally inhibits NaV1.5 expression.

ABSTRACT: Oxidants and canonical Wnt/β-catenin signaling have been shown to decrease cardiac Na(+) channel activity by suppressing NaV1.5 expression. Our aims are to determine if hydrogen peroxide (H2O2), one oxidant of reactive oxygen species (ROS), activates Wnt/β-catenin signaling and promotes β-catenin nuclear activity, leading to suppression of NaV1.5 expression and if this suppression requires the interaction of β-catenin with its nuclear partner, TCF4 (also called TCF7L2) to decrease SCN5a promoter activity. The results demonstrated that H2O2 increased β-catenin, but not TCF4 nuclear localization determined by immunofluorescence without affecting total β-catenin protein level. Furthermore, H2O2 exerted a dose- and time-dependent suppressive effect on NaV1.5 expression. RT-PCR and/or Western b

SUBMITTER: Wang N 

PROVIDER: S-EPMC4912406 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature