Reactive oxygen species (ROS) are oxidizing agents amply implicated in tissue damage. ROS production is inevitably linked to ATP synthesis in most cells, and the rate of production is related to the rate of cell respiration. Multiple antioxidant mechanisms limit ROS dispersion and interaction with cell components, but, when the balance between ROS production and scavenging is lost, oxidative damage develops. Many traits of aging are related to oxidative damage by ROS, including neurodegenerative diseases. Thyroid hormones (THs) are a major factor controlling metabolic and respiratory rates in virtually all cell types in mammals. The general metabolic effect of THs is a relative acceleration of the basal metabolism that includes an increase of the rate of both catabolic and anabolic reactions. THs are related to oxidative stress not only by their stimulation of metabolism but also by their effects on antioxidant mechanisms. Thyroid dysfunction increases with age, so changes in THs levels in the elderly could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear. In this review, we analyze the participation of thyroid hormones on ROS production and oxidative stress, and the way the changes in thyroid status in aging are involved in neurodegenerative diseases.
Susceptibility of MDR A. baumannii to a variety of antibiotics was enhanced in the presence of ellagic and tannic acids. The use of such plant compounds might provide effective treatments for resistant Gram-negative bacterial infections.
The serine protease inhibitor (SERPIN) family member corticosteroid-binding globulin (CBG) is the main carrier of glucocorticoids in plasma. Human CBG mediates the targeted release of cortisol at sites of inflammation through cleavage of its reactive center loop (RCL) by neutrophil elastase. The RCLs of SERPIN family members are targeted by diverse endogenous and exogenous proteases, including several bacterial proteases. We tested different bacteria for their ability to secrete proteases that disrupt CBG cortisol-binding activity, and characterized the responsible protease and site of CBG cleavage. Serum CBG integrity was assessed by Western blotting and cortisol-binding capacity assay. Effects of time, pH, temperature, and protease inhibitors were tested. Proteolytically active proteins from bacterial media were purified by fast protein liquid chromatography, and the active protease and CBG cleavage sites were identified by mass spectrometry. Among the bacteria tested, medium from Pseudomonas aeruginosa actively disrupted the cortisol-binding activity of CBG. This proteolytic activity was inhibited by zinc chelators and occurred most efficiently at pH 7 and elevated physiological temperature (ie, 41°C). Mass spectrometric analysis of a semi-purified fraction of P. aeruginosa media identified the virulence factor LasB as the responsible protease, and this was confirmed by assaying media from LasB-deficient P. aeruginosa. This metalloprotease cleaves the CBG RCL at a major site, distinct from that targeted by neutrophil elastase. Our results suggest that humoral responses to P. aeruginosa infection are influenced by this pathogen's ability to secrete a protease that promotes the release of the anti-inflammatory steroid, cortisol, from its plasma transport protein.
Four new undecose nucleosides (herbicidin
congeners), three known
herbicidins, and 9-(β-d-arabinofuranosyl)hypoxanthine
(Ara-H) were isolated from the organic extract of a fermentation culture
of Streptomyces sp. L-9-10 using proton NMR-guided
fractionation. Their structures were elucidated on the basis of comprehensive
1D and 2D NMR and mass spectrometry analyses. These structures included
2′-O-demethylherbicidin F (1),
9′-deoxy-8′,8′-dihydroxyherbicidin B (2), 9′-deoxy-8′-oxoherbicidin B (2a), and
the 8′-epimer of herbicidin B (3). This is the
first detailed assignment of proton and carbon chemical shifts for
herbicidins A, B, and F. The isolated compounds were evaluated for
cancer chemopreventive potential based on inhibition of tumor necrosis
factor alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB)
activity.
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