Proteasome functional insufficiency activates the calcineurin-NFAT pathway in cardiomyocytes and promotes maladaptive remodelling of stressed mouse hearts.

ABSTRACT:

Aims

Proteasome functional insufficiency (PFI) may play an important role in the progression of congestive heart failure but the underlying molecular mechanism is poorly understood. Calcineurin and nuclear factor of activated T-cells (NFAT) are degraded by the proteasome, and the calcineurin-NFAT pathway mediates cardiac remodelling. The present study examined the hypothesis that PFI activates the calcineurin-NFAT pathway and promotes maladaptive remodelling of the heart.

Methods and results

Using a reporter gene assay, we found that pharmacological inhibition of 20S proteasomes stimulated NFAT transactivation in both mouse hearts and cultured adult mouse cardiomyocytes. Proteasome inhibition stimulated NFAT nuclear translocation in a calcineurin-dependent manner and led to

SUBMITTER: Tang M 

PROVIDER: S-EPMC2972684 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature