scholarly journals Reactive Oxygen Species, Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

2015 ◽  
Vol 8 (2) ◽  
pp. 151-175 ◽  
Author(s):  
Babatunji Oyinloye ◽  
Abiola Adenowo ◽  
Abidemi Kappo
Keyword(s):  
Reactive Oxygen Species ◽  
Antimicrobial Peptides ◽  
Inflammatory Diseases ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Cathelicidin Peptides Restrict Bacterial Growth via Membrane Perturbation and Induction of Reactive Oxygen Species

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Dean A. Rowe-Magnus ◽  
Adenine Y. Kao ◽  
Antonio Cembellin Prieto ◽  
Meng Pu ◽  
Cheng Kao
Keyword(s):  
Reactive Oxygen Species ◽  
Antimicrobial Peptides ◽  
Single Cell ◽  
Reactive Oxygen ◽  
Cellular Damage ◽  
Primary Effect ◽  
Gram Negative Bacteria ◽  
Oxygen Species ◽  
Gram Positive ◽  
Gram Negative

ABSTRACT All metazoans produce antimicrobial peptides (AMPs) that have both broad antimicrobial and immunomodulatory activity. Cathelicidins are AMPs that preferentially kill Gram-negative bacteria in vitro, purportedly by assembling into higher-order structures that perforate the membrane. We utilized high-resolution, single-cell fluorescence microscopy to examine their mechanism of action in real time. Engineered cathelicidins rapidly bound to Gram-negative and Gram-positive cells and penetrated the cytoplasmic membrane. Rapid failure of the peptidoglycan superstructure in regions of active turnover caused leakage of cytoplasmic contents and the formation of membrane-bound blebs. A mutation anticipated to destabilize interactions between cathelicidin subunits had no effect on bactericidal activity, suggesting that cathelicidins have activities beyond perforating the membrane. Nanomolar concentrations of cathelicidins, although not bactericidal, reduced the growth rate of Gram-negative and Gram-positive bacteria. The cells exhibited expression changes in multiple essential processes, including protein synthesis, peptidoglycan biosynthesis, respiration, and the detoxification of reactive oxygen species (ROS). Time-lapse imaging revealed that ROS accumulation preceded bleb formation, and treatments that reduced cellular ROS levels overcame these bactericidal effects. We propose that that the primary effect of cathelicidins is to induce the production of ROS that damage bacterial molecules, leading to slowed growth or cell death. Given their low circulating levels in vivo, AMPs may serve to slow bacterial population expansion so that cellular immunity systems can respond to and battle the infection. IMPORTANCE Antimicrobial peptides (AMPs) are an important part of the mammalian innate immune system in the battle against microbial infection. How AMPs function to control bacteria is not clear, as nearly all activity studies use nonphysiological levels of AMPs. We monitored peptide action in live bacterial cells over short time frames with single-cell resolution and found that the primary effect of cathelicidin peptides is to increase the production of oxidative molecules that cause cellular damage in Gram-positive and Gram-negative bacteria.

scholarly journals APOCYNIN, AN INHIBITOR OF THE NADPH OXIDASE COMPLEX

2020 ◽  
Vol 17 (34) ◽  
pp. 478-501
Author(s):  
Camila Nascimento GIONGO ◽  
Vanessa Falchetti LOPES ◽  
Diana Fortkamp GRIGOLETTO ◽  
Eduardo Hösel MIRANDA
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Reactive Oxygen ◽  
Enzyme Complex ◽  
Oxygen Species ◽  
Phagocytic Cells ◽  
Oxidative Species

Apocynin is a phenolic compound isolated from the plant Picrorhiza kurroa Royle ex Benth. Such a compound has been extensively investigated for its therapeutic potential in diseases involving inflammatory processes or oxidative stress due to its ability to inhibit the NADPH oxidase multienzyme complex. This complex consists of two transmembrane proteins (Nox2 and p22phox) and four cytosolic regulatory proteins (p67phox, p47phox, p40phox, and GTPase-Rac) and their activation occurs after the stimulation of phagocytic cells by the mediation of the enzyme myeloperoxidase (MPO). NADPH oxidase is the only enzyme complex that is intended for the production of superoxide anion that is precursor of highly oxidizing substances classified as reactive oxygen species (ROS). NADPH oxidase is an enzyme complex that produces superoxide anion from molecular oxygen. Ta the same time, the superoxide anion is a precursor to reactive oxygen species (ROS) catalyzed by enzymes.These oxidative species, when in excess, can induce burst, causing irreparable tissue damage. They can act by modifying the redox state of DNA, protein or lipid molecules, playing a central role in the development of chronic pathologies and various health complications. One can cite vascular problems, hyperglycemia, diabetes, hypertension, Alzheimer's disease, and cancer, among others. Apocynin, previously activated by MPO, blocks the enzyme complex and prevents the formation of these oxidative species. Therefore, the central biological function of compound is to modulate the action of NADPH oxidase, promoting a positive effect in the prevention/remediation of inflammatory diseases.

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