Shear behavior of bovine scleral tissue.

Ocular tissue properties have been widely studied in tension and compression for humans and a variety of animals. However, direct shear testing of the tissues of the sclera appear to be absent from the literature even though modeling, analyses, and anatomical studies have indicated that shear may play a role in the etiology of primary open angle glaucoma (POAG). In this work, the mechanical behavior of bovine scleral tissue in shear has been studied in both out-of-plane and in-plane modes of deformation.

PECAM-1 and caveolae form the mechanosensing complex necessary for NOX2 activation and angiogenic signaling with stopped flow in pulmonary endothelium.

We showed that stop of flow triggers a mechanosignaling cascade that leads to the generation of reactive oxygen species (ROS); however, a mechanosensor coupled to the cytoskeleton that could potentially transduce flow stimulus has not been identified. We showed a role for KATP channel, caveolae (caveolin-1), and NADPH oxidase 2 (NOX2) in ROS production with stop of flow. Based on reports of a mechanosensory complex that includes platelet endothelial cell adhesion molecule-1 (PECAM-1) and initiates signaling with mechanical force, we hypothesized that PECAM-1 could serve as a mechanosensor in sensing disruption of flow.

Mechanotransduction drives post ischemic revascularization through K(ATP) channel closure and production of reactive oxygen species.

Aims: We reported earlier that ischemia results in the generation of reactive oxygen species (ROS) via the closure of a K(ATP) channel which causes membrane depolarization and NADPH oxidase 2 (NOX2) activation. This study was undertaken to understand the role of ischemia-mediated ROS in signaling.

Results: Angiogenic potential of pulmonary microvascular endothelial cells (PMVEC) was studied in vitro and in the hind limb in vivo.

Functional interaction of glutathione S-transferase pi and peroxiredoxin 6 in intact cells.

Peroxiredoxin 6 (Prdx6) is a 1-Cys member of the peroxiredoxin superfamily that plays an important role in antioxidant defense. Glutathionylation of recombinant Prdx6 mediated by π glutathione S-transferase (GST) is required for reduction of the oxidized Cys and completion of the peroxidatic catalytic cycle in vitro. This study investigated the requirement for πGST in intact cells.

Membrane depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS.

Loss of fluid shear stress (ischemia) to the lung endothelium causes endothelial plasma membrane depolarization via ATP-sensitive K(+) (K(ATP)) channel closure, initiating a signaling cascade that leads to NADPH oxidase (NOX2) activation and ROS production. Since wortmannin treatment significantly reduces ROS production with ischemia, we investigated the role of phosphoinositide 3-kinase (PI3K) in shear-associated signaling. Pulmonary microvascular endothelial cells in perfused lungs subjected to abrupt stop of flow showed membrane depolarization and ROS generation.