AMPK activation improves recovery from pneumonia-induced lung injury via reduction of er-stress and apoptosis in alveolar epithelial cells.

Background: Bacterial pneumonia and related lung injury are among the most frequent causes of mortality in intensive care units, but also inflict serious and prolonged respiratory complications among survivors. Given that endoplasmic reticulum (ER) stress is a hallmark of sepsis-related alveolar epithelial cell (AEC) dysfunction, we tested if AMP-activated protein kinase (AMPK) affects recovery from ER stress and apoptosis of AECs during post-bacterial infection.

Methods: In a murine model of lung injury by P.

Echocardiographic, Biochemical, and Electrocardiographic Correlates Associated With Progressive Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive proliferative vasculopathy associated with mechanical and electrical changes, culminating in increased vascular resistance, right ventricular (RV) failure, and death. With a main focus on invasive tools, there has been an underutilization of echocardiography, electrocardiography, and biomarkers to non-invasively assess the changes in myocardial and pulmonary vascular structure and function during the course of PAH. A SU5416-hypoxia rat model was used for inducing PAH.

AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections.

Metabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression.

NOX2 decoy peptides disrupt trauma-mediated neutrophil immunosuppression and protect against lethal peritonitis.

Trauma and sepsis are frequent causes of immunosuppression and risk of secondary bacterial infections and mortality among critically ill patients. Reduced activity of neutrophil NADPH oxidase 2 (NOX2) and impaired bacterial killing are among the major indices of immunosuppression. We hypothesize that NOX2-decoy peptides disrupt the inhibition of neutrophil NOX2 by plasma of patients with severe trauma and immunosuppression, thereby preserving the neutrophil respiratory burst that is a central antimicrobial mechanism.

MicroRNA-mediated inflammation and coagulation effects in rats exposed to an inhaled analog of sulfur mustard.

Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog of sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and coagulation and altered levels of plasma microRNAs (miRNAs). Rats were exposed to aerosolized CEES and euthanized 12 h later for collection of tissue and plasma. Profiling of miRNAs in plasma, using a TaqMan-based RT-PCR array, revealed 14 differentially expressed miRNAs.

Acute pulmonary effects of aerosolized nicotine.

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine-containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown.

Magnesium homeostasis protects Salmonella against nitrooxidative stress.

The PhoPQ two-component regulatory system coordinates the response of Salmonella enterica serovar Typhimurium to diverse environmental challenges encountered during infection of hosts, including changes in Mg concentrations, pH, and antimicrobial peptides. Moreover, PhoPQ-dependent regulation of gene expression promotes intracellular survival of Salmonella in macrophages, and contributes to the resistance of this pathogen to reactive nitrogen species (RNS) generated from the nitric oxide produced by the inducible nitric oxide (NO) synthase of macrophages. We report here that Salmonella strains with mutations of phoPQ are hypersensitive to killing by RNS generated in vitro.

Cytochrome bd-Dependent Bioenergetics and Antinitrosative Defenses in Salmonella Pathogenesis.

Unlabelled: In the course of an infection, Salmonella enterica occupies diverse anatomical sites with various concentrations of oxygen (O) and nitric oxide (NO). These diatomic gases compete for binding to catalytic metal groups of quinol oxidases. Enterobacteriaceae express two evolutionarily distinct classes of quinol oxidases that differ in affinity for O and NO as well as stoichiometry of H translocated across the cytoplasmic membrane.

Antioxidant Defense by Thioredoxin Can Occur Independently of Canonical Thiol-Disulfide Oxidoreductase Enzymatic Activity.

The thiol-disulfide oxidoreductase CXXC catalytic domain of thioredoxin contributes to antioxidant defense in phylogenetically diverse organisms. We find that although the oxidoreductase activity of thioredoxin-1 protects Salmonella enterica serovar Typhimurium from hydrogen peroxide in vitro, it does not appear to contribute to Salmonella's antioxidant defenses in vivo. Nonetheless, thioredoxin-1 defends Salmonella from oxidative stress resulting from NADPH phagocyte oxidase macrophage expression during the innate immune response in mice.

The 4-cysteine zinc-finger motif of the RNA polymerase regulator DksA serves as a thiol switch for sensing oxidative and nitrosative stress.

We show that thiols in the 4-cysteine zinc-finger motif of DksA, an RNA polymerase accessory protein known to regulate the stringent response, sense oxidative and nitrosative stress. Hydrogen peroxide- or nitric oxide (NO)-mediated modifications of thiols in the DksA 4-cysteine zinc-finger motif release the metal cofactor and drive reversible changes in the α-helicity of the protein. Wild-type and relA spoT mutant Salmonella, but not isogenic dksA-deficient bacteria, experience the downregulation of r-protein and amino acid transport expression after NO treatment, suggesting that DksA can regulate gene expression in response to NO congeners independently of the ppGpp alarmone.

Ferric uptake regulator-dependent antinitrosative defenses in Salmonella enterica serovar Typhimurium pathogenesis.

Herein we report an important role for the ferric uptake regulator (Fur) in the resistance of Salmonella enterica serovar Typhimurium to the reactive nitrogen species produced by inducible nitric oxide (NO) synthase in an NRAMP1(r) murine model of acute systemic infection. The expression of fur protected Salmonella grown under normoxic and hypoxic conditions against the bacteriostatic activity of NO. The hypersusceptibility of fur-deficient Salmonella to the cytotoxic actions of NO coincides with a marked repression of respiratory activity and the reduced ability of the bacteria to detoxify NO.

Low-molecular-weight thiol-dependent antioxidant and antinitrosative defences in Salmonella pathogenesis.

We found herein that the intracytoplasmic pool of the low-molecular-weight (LMW) thiol glutathione (GSH) is readily oxidized in Salmonella exposed to nitric oxide (NO). The hypersusceptibility of gshA and gshB mutants lacking γ-glutamylcysteine and glutathione synthetases to NO and S-nitrosoglutathione indicates that GSH antagonizes the bacteriostatic activity of reactive nitrogen species. Metabolites of the GSH biosynthetic pathway do not affect the enzymatic activity of classical NO targets such as quinol oxidases.

Nitric oxide protects bacteria from aminoglycosides by blocking the energy-dependent phases of drug uptake.

Our investigations have identified a mechanism by which exogenous production of nitric oxide (NO) induces resistance of Gram-positive and -negative bacteria to aminoglycosides. An NO donor was found to protect Salmonella spp. against structurally diverse classes of aminoglycosides of the 4,6-disubstituted 2-deoxystreptamine group.

Redox sensor SsrB Cys203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection.

We show herein that the Salmonella pathogenicity island 2 (SPI2) response regulator SsrB undergoes S-nitrosylation upon exposure of Salmonella to acidified nitrite, a signal encountered by this enteropathogen in phagosomes of macrophages. Mutational analysis has identified Cys(203) in the C-terminal dimerization domain of SsrB as the redox-active residue responding to nitric oxide (NO) congeners generated in the acidification of nitrite. Peroxynitrite and products of the autooxidation of NO in the presence of oxygen, but not hydrogen peroxide, inhibit the DNA-binding capacity of SsrB, demonstrating the selectivity of the reaction of Cys(203) with reactive nitrogen species (RNS).

Remediation and treatment of organopollutants mediated by peroxidases: a review.

In this paper an effort has been made to review the literature on the role of peroxidases in the remediation and treatment of a wide spectrum of aromatic pollutants. Peroxidases can catalyse degradation/transformation of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorines, 2,4,6-trinitrotoluene, phenolic compounds and dyes. These enzymes are also capable of treating various types of recalcitrant aromatic compounds in the presence of redox mediators.

Altered platelet monoamine oxidase-B activity in idiopathic Parkinson's disease.

A case-control study was undertaken to investigate the status of platelet monoamine oxidase-B (MAO-B) activity in Indian cases of idiopathic Parkinson's disease. A significant increase in the activity of platelet MAO-B was observed in Parkinson's cases (n = 26) as compared to controls (n = 26). No significant change in the activity of the enzyme was observed while the data was analysed with respect to age, sex and duration of disease.

Nitric oxide evokes an adaptive response to oxidative stress by arresting respiration.

Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components of the electron transport chain (ETC). Basal levels of oxidative stress can dramatically rise upon activation of the NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms express a battery of low-molecular-weight thiol scavengers, a legion of detoxifying catalases, peroxidases, and superoxide dismutases, as well as a variety of repair systems.

N(2)O(3) enhances the nitrosative potential of IFNgamma-primed macrophages in response to Salmonella.

We show here that the nitric oxide (NO)-detoxifying Hmp flavohemoprotein increases by 3-fold the transcription of the Salmonella pathogenicity island 2 (SPI2) in macrophages expressing a functional inducible NO synthase (iNOS). However, Hmp does not prevent NO-related repression of SPI2 transcription in IFNgamma-primed phagocytes, despite preserving intracellular transcription of sdhA sdhB subunits of Salmonella succinate dehydrogenase within both control and IFNgamma-primed phagocytes. To shed light into the seemingly paradoxical role that Hmp plays in protecting intracellular SPI2 expression in various populations of macrophages, N(2)O(3) was quantified as an indicator of the nitrosative potential of Salmonella-infected phagocytes in different states of activation.

Synergistic activities of moxifloxacin combined with piperacillin-tazobactam or cefepime against Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii clinical isolates.

The bactericidal activity of moxifloxacin alone and in combination with cefepime or piperacillin-tazobactam against clinical isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii was evaluated by using time-kill methods and antimicrobial concentrations of one-half and one times the MIC. Synergy was observed in 58 to 88% of the strains and resulted in bactericidal activity against 60 to 100% of the strains. Combinations including moxifloxacin demonstrated enhanced bactericidal activity compared with that of either agent tested alone.