Phosphorylation of CHOP (C/EBP Homologous Protein) by the AMP-Activated Protein Kinase Alpha 1 in Macrophages Promotes CHOP Degradation and Reduces Injury-Induced Neointimal Disruption In Vivo.

ABSTRACT:

Rationale

Elevated levels of CHOP (C/EBP homologous protein), a member of the C/EBP transcription factor family, in advanced atherosclerotic plaques is reported to be associated with atherosclerotic plaque rupture in humans. However, the molecular mechanism by which CHOP accumulation occurs is poorly defined.

Objective

The aim of this study was to investigate if (1) macrophage AMPK (AMP-activated protein kinase) regulates cellular CHOP accumulation and (2) whole-body Ampk deletion leads to neointimal disruption.

Methods and results

In isolated or cultured macrophages, Ampkα1 deletion markedly increased apoptosis and CHOP, whereas pharmacological activation of AMPK dramatically reduced CHOP protein level via promoting CHOP degradation by proteasome. In addition, cotran

SUBMITTER: Dai X 

PROVIDER: S-EPMC5085850 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature