The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro.

The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30-300nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30-300nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications

Effect of Fibrin Glue on the Biomechanical Properties of Human Descemet's Membrane

10.1371/journal.pone.0037456PLoS ONE75

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Analysis methods for multi-component wave measurements on board the DEMETER spacecraft

International audienceWe describe analysis methods to estimate parameters of electromagnetic waves based on the multi-component measurements of the DEMETER spacecraft. Using the fact that the wave magnetic field is perpendicular to the wave vector, the wave normal direction can be estimated by different methods. We use these plane-wave estimates to interpret measurements of the observed wave emissions. For instance, we use the recently developed singular value decomposition (SVD) technique. The results of the plane-wave analysis have an advantage that they often allow a straightforward interpretation. These different methods have been successfully tested with the data of previous spacecraft. All these methods are also implemented in the analysis tools designed for the analysis of the DEMETER wave measurements.We show the first results of these analysis techniques for different types of wave emissions observed on board DEMETER. Obliquely propagating right-hand polarized electromagnetic waves at a few hundreds of Hz are usually connected with a multi-ion mode structure below the local proton cyclotron frequency and with a sharp lower cutoff of left-hand polarized waves, as well as with right-hand polarized waves tunelling below the multi-ion cross-over frequency. Electron and proton whistlers are also very frequently observed on DEMETER. An unusual narrow-band emission at 140 Hz (well below the local proton cyclotron frequency) serves us as another case for a detailed analysis. We find that these waves are right-hand polarized and obliquely propagating.Using this example case, we also present analysis methods to estimate continuous distribution of wave energy density as a function of wave vector directions. These techniques of wave distribution function (WDF) analysis need both wave and particle measurements. In the analyzed case, two different methods of WDF analysis give similar results consistent with the results of the plane-wave techniques. To identify the source region we use the backward ray-tracing method. The wave normal direction obtained by the analysis of multi-component data is used for a simulation of wave propagation from the point of measurement. By this procedure, we obtain an inverse trajectory of the wave ray. We can thus follow the ray path back to the anticipated source region which is in our case located a few degrees of latitude to the South from the spacecraft position