Suppression of the JNK pathway by induction of a metabolic stress response prevents vascular injury and dysfunction.

ABSTRACT:

Background

Oxidative injury and dysfunction of the vascular endothelium are early and causal features of many vascular diseases. Single antioxidant strategies to prevent vascular injury have met with mixed results.

Methods and results

Here, we report that induction of a metabolic stress response with adenosine monophosphate kinase (AMPK) prevents oxidative endothelial cell injury. This response is characterized by stabilization of the mitochondrion and increased mitochondrial biogenesis, resulting in attenuation of oxidative c-Jun N-terminal kinase (JNK) activation. We report that peroxisome proliferator coactivator 1alpha is a key downstream target of AMPK that is both necessary and sufficient for the metabolic stress response and JNK attenuation. Moreover, induction of the

SUBMITTER: Schulz E 

PROVIDER: S-EPMC2756193 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature