scholarly journals ‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 915
Author(s):  
Hannah M. Southam ◽  
Michael P. Williamson ◽  
Jonathan A. Chapman ◽  
Rhiannon L. Lyon ◽  
Clare R. Trevitt ◽  
...  
Keyword(s):  
Amino Acids ◽  
Carbon Monoxide ◽  
Mammalian Cells ◽  
Reduced Glutathione ◽  
Biological Effects ◽  
Significant Loss ◽  
Binding Affinities ◽  
Strong Negative Correlation ◽  
Inhibition Of Growth ◽  
Intracellular Target

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological ‘gasotransmitter’, in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release. Here, we investigate the basis of its potent antibacterial activity against Escherichia coli and demonstrate, using three globin CO sensors, that CORM-2 releases negligible CO (<0.1 mol CO per mol CORM-2). A strong negative correlation between viability and cellular ruthenium accumulation implies that ruthenium toxicity underlies biocidal activity. Exogenous amino acids and thiols (especially cysteine, glutathione and N-acetyl cysteine) protected bacteria against inhibition of growth by CORM-2. Bacteria treated with 30 μM CORM-2, with added cysteine and histidine, exhibited no significant loss of viability, but were killed in the absence of these amino acids. Their prevention of toxicity correlates with their CORM-2-binding affinities (Cys, Kd 3 μM; His, Kd 130 μM) as determined by 1H-NMR. Glutathione is proposed to be an important intracellular target of CORM-2, with CORM-2 having a much higher affinity for reduced glutathione (GSH) than oxidised glutathione (GSSG) (GSH, Kd 2 μM; GSSG, Kd 25,000 μM). The toxicity of low, but potent, levels (15 μM) of CORM-2 was accompanied by cell lysis, as judged by the release of cytoplasmic ATP pools. The biological effects of CORM-2 and related CORMs, and the design of biological experiments, must be re-examined in the light of these data.

Ultrastructural Changes in Three Different Mammalian Cells Following Ultraviolet Laser Irradiation

1972 ◽  
Vol 30 ◽  
pp. 350-351
Author(s):  
K. Shankar Narayan ◽  
Kailash C. Gupta ◽  
Tohru Okigaki
Keyword(s):  
Ultraviolet Light ◽  
Mammalian Cells ◽  
Biological Effects ◽  
Survival Rates ◽  
Chinese Hamster ◽  
Cell Types ◽  
Differential Sensitivity ◽  
Ultrastructural Changes ◽  
Ultraviolet Laser

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.

Vasopressin and oxytocin analogs with interchanged sequence of amino acids in positions 7 and 8. synthesis and biological effects

1981 ◽  
Vol 46 (9) ◽  
pp. 2136-2139 ◽  
Author(s):  
Ivo Bláha ◽  
Viktor Krchňák ◽  
Milan Zaoral
Keyword(s):  
Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Effects ◽  
Free Flow ◽  
Protecting Groups ◽  
Pressor Effect ◽  
Phase Synthesis ◽  
Antidiuretic Effect

p-Toluenesulfonyl-S-benzylcysteinyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-NG-p-toluenesulfanylarginyl-prolyl-glycineamide (I) and S-benzylcysteinyl-tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-benzylcysteinyl-leucyl-prolyl-glycine amide (III) were prepared by solid phase synthesis. After removal of the protecting groups, closure of the disulfide ring, and purification by continuous free-flow electrophoresis [arginine7, proline8]vasopressin (II) and [leucine7, proline8]oxytocin (IV) were obtained. The antidiuretic effect of II is markedly higher than its pressor effect; IV possesses c. 6% of the uterotonic and c. 10% of the galactogogous effect of oxytocin.

scholarly journals Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 957
Author(s):  
Mamona Nazir ◽  
Muhammad Saleem ◽  
Muhammad Imran Tousif ◽  
Muhammad Aijaz Anwar ◽  
Frank Surup ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Biological Effects ◽  
Structural Diversity ◽  
Chemical Diversity ◽  
Biosynthetic Pathways ◽  
Natural Sources ◽  
Hybrid Compounds ◽  
Anti Inflammatory

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

scholarly journals Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 481
Author(s):  
Gemma G. Martínez-García ◽  
Raúl F. Pérez ◽  
Álvaro F. Fernández ◽  
Sylvere Durand ◽  
Guido Kroemer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Mammalian Cells ◽  
Tissue Homeostasis ◽  
In Vivo Studies ◽  
Protective Mechanism ◽  
Cardiac Damage ◽  
Wide Range ◽  
First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

scholarly journals ANTIPODAL SPECIFICITY IN THE INHIBITION OF GROWTH OF ESCHERICHIA COLI BY AMINO ACIDS

1948 ◽  
Vol 174 (2) ◽  
pp. 391-398
Author(s):  
Yutaka. Kobayashi ◽  
Marguerite. Fling ◽  
Sidney W. Fox
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Inhibition Of Growth

scholarly journals Distinct Chemistries Define the Diverse Biological Effects of Plasma Activated Water Generated with Spark and Glow Plasma Discharges

2021 ◽  
Vol 11 (3) ◽  
pp. 1178
Author(s):  
Evanthia Tsoukou ◽  
Maxime Delit ◽  
Louise Treint ◽  
Paula Bourke ◽  
Daniela Boehm
Keyword(s):  
Mammalian Cells ◽  
Biomedical Application ◽  
Biological Effects ◽  
Mode Of Delivery ◽  
Chemical Species ◽  
Resistant Bacteria ◽  
Cytotoxic Activities ◽  
Promising Alternative ◽  
Plasma Activated Water

The spread of multidrug-resistant bacteria poses a significant threat to human health. Plasma activated liquids (PAL) could be a promising alternative for microbial decontamination, where different PAL can possess diverse antimicrobial efficacies and cytotoxic profiles, depending on the range and concentration of their reactive chemical species. In this research, the biological activity of plasma activated water (PAW) on different biological targets including both microbiological and mammalian cells was investigated in vitro. The aim was to further an understanding of the specific role of distinct plasma reactive species, which is required to tailor plasma activated liquids for use in applications where high antimicrobial activity is required without adversely affecting the biology of eukaryotic cells. PAW was generated by glow and spark discharges, which provide selective generation of hydrogen peroxide, nitrite and nitrate in the liquid. The PAW made by either spark or glow discharges showed similar antimicrobial efficacy and stability of activity, despite the very different reactive oxygen species (ROS) and reactive nitrogen species profiles (RNS). However, different trends were observed for cytotoxic activities and effects on enzyme function, which were translated through the selective chemical species generation. These findings indicate very distinct mechanisms of action which may be exploited when tailoring plasma activated liquids to various applications. A remarkable stability to heat and pressure was noted for PAW generated with this set up, which broadens the application potential. These features also suggest that post plasma modifications and post generation stability can be harnessed as a further means of modulating the chemistry, activity and mode of delivery of plasma functionalised liquids. Overall, these results further understanding on how PAL generation may be tuned to provide candidate disinfectant agents for biomedical application or for bio-decontamination in diverse areas.

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