Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability.

Disulfide bonds play a key role in stabilizing protein structures, with disruption strongly associated with loss of protein function and activity. Previous data have suggested that disulfides show only modest reactivity with oxidants. In the current study, we report kinetic data indicating that selected disulfides react extremely rapidly, with a variation of 10 in rate constants.

A Nitric Oxide Storage and Transport System That Protects Activated Macrophages from Endogenous Nitric Oxide Cytotoxicity.

Nitric oxide (NO) is integral to macrophage cytotoxicity against tumors due to its ability to induce iron release from cancer cells. However, the mechanism for how activated macrophages protect themselves from endogenous NO remains unknown. We previously demonstrated by using tumor cells that glutathione S-transferase P1 (GSTP1) sequesters NO as dinitrosyl-dithiol iron complexes (DNICs) and inhibits NO-mediated iron release from cells via the transporter multidrug resistance protein 1 (MRP1/ABCC1).

Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development.

Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (λ 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation.

The protective effect of apolipoprotein in models of trophoblast invasion and preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy. It is associated with abnormal placentation via poor placental invasion of the uterine vasculature by trophoblast cells, leading to poor placental perfusion, oxidative stress, and inflammation, all of which are implicated in its pathogenesis. A dyslipidemia characterized by low plasma levels of high-density lipoproteins (HDL) and elevated triglycerides has been described in preeclampsia.

Phrenic nerve deficits and neurological immunopathology associated with acute West Nile virus infection in mice and hamsters.

Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography.

Androgen Receptor-Mediated Genomic Androgen Action Augments Ischemia-Induced Neovascularization.

Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of genomic androgen action mediated by androgen receptor (AR), a ligand-activated nuclear transcription factor, remains poorly understood. Using an AR knockout (KO) mouse strain that contains a transcriptionally inactive AR (ARKO), we examined the role of AR genomic function in modulating androgen-mediated augmentation of ischemia-induced neovascularization.

Substrate-Regulated Growth of Plasma-Polymerized Films on Carbide-Forming Metals.

Although plasma polymerization is traditionally considered as a substrate-independent process, we present evidence that the propensity of a substrate to form carbide bonds regulates the growth mechanisms of plasma polymer (PP) films. The manner by which the first layers of PP films grow determines the adhesion and robustness of the film. Zirconium, titanium, and silicon substrates were used to study the early stages of PP film formation from a mixture of acetylene, nitrogen, and argon precursor gases.

Reconstituted high-density lipoproteins promote wound repair and blood flow recovery in response to ischemia in aged mice.

Background: The average population age is increasing and the incidence of age-related vascular complications is rising in parallel. Impaired wound healing and disordered ischemia-mediated angiogenesis are key contributors to age-impaired vascular complications that can lead to amputation. High-density lipoproteins (HDL) have vasculo-protective properties and augment ischemia-driven angiogenesis in young animals.

Plasma Ion Activated Expanded Polytetrafluoroethylene Vascular Grafts with a Covalently Immobilized Recombinant Human Tropoelastin Coating Reducing Neointimal Hyperplasia.

Expanded polytetrafluoroethylene (ePTFE) vascular conduits with less than or equal to 6 mm internal diameter typically occlude due to a combination of thrombus formation and neointimal hyperplasia. We hypothesized that by layering the polymerized elastin precursor, human tropoelastin, in the synthetic vessel lumen we could mimic the internal elastic lamina and so maintain low thrombogenicity while significantly reducing smooth muscle cell proliferation. The luminal surfaces of ePTFE conduits were activated with plasma immersion ion implantation (PIII) treatment to facilitate covalent attachment of tropoelastin.

A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan.

Background: Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan.

Peroxynitrite-mediated oxidation of plasma fibronectin.

Fibronectin is a large dimeric glycoprotein present in both human plasma and in basement membranes. The latter are specialized extracellular matrices underlying endothelial cells in the artery wall. Peroxynitrous acid (ONOOH) a potent oxidizing and nitrating agent, is formed in vivo from superoxide and nitric oxide radicals by stimulated macrophages and other cells.

High-Density Lipoproteins Rescue Diabetes-Impaired Angiogenesis via Scavenger Receptor Class B Type I.

Disordered neovascularization and impaired wound healing are important contributors to diabetic vascular complications. We recently showed that high-density lipoproteins (HDLs) enhance ischemia-mediated neovascularization, and mounting evidence suggests HDL have antidiabetic properties. We therefore hypothesized that HDL rescue diabetes-impaired neovascularization.

Microglial number is related to the number of tyrosine hydroxylase neurons in SHR and normotensive rats.

Microglia are ubiquitously distributed throughout the central nervous system (CNS) and play a critical role in the maintenance of neuronal homeostasis. Recent advances have shown that microglia, never resting cells of the CNS, continuously monitor and influence neuronal/synaptic activity levels, by communicating with neurons with the aid of their dynamic processes. The brainstem contains many catecholaminergic nuclei that are key to many aspects of brain function.

Plaque stabilizing effects of apolipoprotein A-IV.

Background And Aims: Apolipoprotein (apo) A-IV, the third most abundant HDL-associated protein, is atheroprotective and shares similar properties as apoA-I. We have reported previously that apoA-I, the most abundant apolipoprotein in HDL, inhibits plaque disruption in a mouse model. We aimed at examining the effects of apoA-IV on markers of plaque stability in vivo.

Tropoelastin enhances nitric oxide production by endothelial cells.

Aims: This study aimed to characterize the role of tropoelastin in eliciting a nitric oxide response in endothelial cells.

Materials And Methods: Nitric oxide production in cells was quantified following the addition of known nitric oxide synthase pathway inhibitors such as LNAME and 1400W. The effect of eNOS siRNA knockdowns was studied using western blotting and assessed in the presence of PI3K-inhibitor, wortmannin.

Dynamic changes in the relationship of microglia to cardiovascular neurons in response to increases and decreases in blood pressure.

Microglia are present throughout the central nervous system (CNS) and express receptors for every known neurotransmitter. During inflammation, microglia change into a state that either promotes removal of debris (M1), or into a state that promotes soothing (M2). Caudal- and rostral- ventrolateral medullary regions (CVLM and RVLM, respectively) of the brainstem are key nuclei involved in all aspects of the cardiovascular system.

Carbohydrate ingestion induces sex-specific cardiac vagal inhibition, but not vascular sympathetic modulation, in healthy older women.

The role of vagal function in cardiovascular risk in older women remains unclear. Autonomic modulation following carbohydrate ingestion (CI) and postural stress (PS) were investigated in 14 healthy men and 21 age-matched postmenopausal women (age: 65.0 ± 2.

Chasing great paths of Helmut Sies "Oxidative Stress".

Prof. Dr. Helmut Sies is a pioneer of "Oxidative Stress", and has published over 18 papers with the name of "Oxidative Stress" in the title.

Plasma-Activated Tropoelastin Functionalization of Zirconium for Improved Bone Cell Response.

The mechanical strength, durability, corrosion resistance, and biocompatibility of metal alloys based on zirconium (Zr) and titanium (Ti) make them desirable materials for orthopedic implants. However, as bioinert metals, they do not actively promote bone formation and integration. Here we report a plasma coating process for improving integration of such metal implants with local bone tissue.

Intermittent hypoxia-induced cardiorespiratory long-term facilitation: A new role for microglia.

Intermittent hypoxia induces plasticity in neural networks controlling breathing and cardiovascular function. Studies demonstrate that mechanisms causing cardiorespiratory plasticity rely on intracellular signalling pathways that are activated by specific neurotransmitters. Peptides such as serotonin, PACAP and orexin are well-known for their physiological significance in regulating the cardiorespiratory system.

Mechanically Robust Plasma-Activated Interfaces Optimized for Vascular Stent Applications.

The long-term performance of many medical implants is limited by the use of inherently incompatible and bioinert materials. Metallic alloys, ceramics, and polymers commonly used in cardiovascular devices encourage clot formation and fail to promote the appropriate molecular signaling required for complete implant integration. Surface coating strategies have been proposed for these materials, but coronary stents are particularly problematic as the large surface deformations they experience in deployment require a mechanically robust coating interface.

Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly.

The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures.

Cellular targets of the myeloperoxidase-derived oxidant hypothiocyanous acid (HOSCN) and its role in the inhibition of glycolysis in macrophages.

Myeloperoxidase (MPO) released at sites of inflammation catalyzes the formation of the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from H2O2 and halide and pseudo-halide ions. HOCl, a major oxidant produced under physiological conditions reacts rapidly with many biological molecules, and is strongly linked with tissue damage during inflammatory disease. The role of HOSCN in disease is less clear, though it can initiate cellular damage by pathways involving the selective oxidation of thiol-containing proteins.

Blended Polyurethane and Tropoelastin as a Novel Class of Biologically Interactive Elastomer.

Polyurethanes are versatile elastomers but suffer from biological limitations such as poor control over cell attachment and the associated disadvantages of increased fibrosis. We address this problem by presenting a novel strategy that retains elasticity while modulating biological performance. We describe a new biomaterial that comprises a blend of synthetic and natural elastomers: the biostable polyurethane Elast-Eon and the recombinant human tropoelastin protein.