Role of growth arrest and DNA damage-inducible α in Akt phosphorylation and ubiquitination after mechanical stress-induced vascular injury.

ABSTRACT:

Rationale

The stress-induced growth arrest and DNA damage-inducible a (GADD45a) gene is up-regulated by mechanical stress with GADD45a knockout (GADD45a(-/-)) mice demonstrating both increased susceptibility to ventilator-induced lung injury (VILI) and reduced levels of the cell survival and vascular permeability signaling effector (Akt). However, the functional role of GADD45a in the pathogenesis of VILI is unknown.

Objectives

We sought to define the role of GADD45a in the regulation of Akt activation induced by mechanical stress.

Methods

VILI-challenged GADD45a(-/-) mice were administered a constitutively active Akt1 vector and injury was assessed by bronchoalveolar lavage cell counts and protein levels. Human pulmonary artery endothelial cells (EC) were exposed to

SUBMITTER: Mitra S 

PROVIDER: S-EPMC3763933 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature