Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

Comparison of free radical generation by pre- and post-sintered cemented carbide particles.

Rapid generation of reactive oxygen species (ROS) may occur in response to cellular contact with metal particles. Generation of ROS by cobalt and/or tungsten carbide is implicated in causing hard metal lung disease (HMD) and allergic contact dermatitis (ACD). In this study, ROS generation and particle properties that influence radical generation were assessed for three sizes of tungsten, tungsten carbide, cobalt, admixture (tungsten carbide and cobalt powders), spray dryer, and post-sintered chamfer grinder powders using chemical (H(2)O(2) plus phosphate buffered saline, artificial lung surfactant, or artificial sweat) and cellular (RAW 264.7 mouse peritoneal monocytes plus artificial lung surfactant) reaction systems. For a given material, on a mass basis, hydroxyl (.OH) generation generally increased as particle size decreased; however, on a surface area basis, radical generation levels were more, but not completely, similar. Chamfer grinder powder, polycrystalline aggregates of tungsten carbide in a metallic cobalt matrix, generated the highest levels of .OH radicals (p < 0.05). Radical generation was not dependent on the masses of metals, rather, it involved surface-chemistry-mediated reactions that were limited to a biologically active fraction of the total available surface area of each material. Improved understanding of particle surface chemistry elucidated the importance of biologically active surface area in generation of ROS by particle mixtures.

Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations.

Diabetic cardiomyopathy is the leading cause of heart failure among diabetic patients, and mitochondrial dysfunction has been implicated as an underlying cause in the pathogenesis. Cardiac mitochondria consist of two spatially, functionally, and morphologically distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). SSM are situated beneath the plasma membrane, whereas IFM are embedded between myofibrils. The goal of this study was to determine whether spatially distinct cardiac mitochondrial subpopulations respond differently to a diabetic phenotype. Swiss-Webster mice were subjected to intraperitoneal injections of streptozotocin or citrate saline vehicle. Five weeks after injections, diabetic hearts displayed decreased rates of contraction, relaxation, and left ventricular developed pressures (P < 0.05 for all three). Both mitochondrial size (forward scatter, P < 0.01) and complexity (side scatter, P < 0.01) were decreased in diabetic IFM but not diabetic SSM. Electron transport chain complex II respiration was decreased in diabetic SSM (P < 0.05) and diabetic IFM (P < 0.01), with the decrease being greater in IFM. Furthermore, IFM complex I respiration and complex III activity were decreased with diabetes (P < 0.01) but were unchanged in SSM. Superoxide production was increased only in diabetic IFM (P < 0.01). Oxidative damage to proteins and lipids, indexed through nitrotyrosine residues and lipid peroxidation, were higher in diabetic IFM (P < 0.05 and P < 0.01, respectively). The mitochondria-specific phospholipid cardiolipin was decreased in diabetic IFM (P < 0.01) but not SSM. These results indicate that diabetes mellitus imposes a greater stress on the IFM subpopulation, which is associated, in part, with increased superoxide generation and oxidative damage, resulting in morphological and functional abnormalities that may contribute to the pathogenesis of diabetic cardiomyopathy.