https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

Free radicals, metals and antioxidants in oxidative stress-induced cancer

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

/pdf/nitric-oxide-and-peroxynitrite-in-health-and-disease-3uuuqgfdcz.pdf

Nitric Oxide and Peroxynitrite in Health and Disease

WITH increasing frequency, the human neutrophil is being implicated as a mediator of tissue-destructive events in inflammatory diseases ranging from rheumatoid arthritis and myocardial reperfusion injury to respiratory distress syndromes, blistering skin disorders, and ulcerative colitis.1 , 2 In each of these diseases, as well as a variety of other acute inflammatory disorders, important components of these pathologic processes are being linked to the neutrophil's ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissues. Although these toxins normally defend the host against invading microbes, the neutrophil has little intrinsic ability to differentiate between foreign . . .

Tissue Destruction by Neutrophils

Role of the Enteric Microbiota in Intestinal Homeostasis and Inflammation

Interferon-γ and Interleukin-10 Reciprocally Regulate Endothelial Junction Integrity and Barrier Function

Publisher Summary The multiple effects of nitric oxide (NO) in biological systems have resulted in intense investigation into the mechanisms of NO-mediated events. The chemistry of NO is the primary determinant of its biological properties. However, not all the reactions of NO that can be performed in test tube are pertinent in vivo. This chapter provides a guide through the diverse reactions of NO in biological systems. The scheme of the chemical biology of NO divides the reactions into the two categories of direct and indirect effects. Direct effects are defined as those reactions that are fast enough to occur between NO and specific biological targets. Indirect effects do not involve NO, but rather, are mediated by reactive NO species formed from the reaction of NO with either oxygen or superoxide. These species can mediate either nitrosative or oxidative stress. Aspects of the chemical biology of NO relating to biological molecules such as guanylate cyclase, cytochrome P-450, nitric oxide synthase, catalase, and DNA are reviewed and the possible roles NO performs in different biological situations are explored.

The Chemical Biology of Nitric Oxide

Dynamic state of S-nitrosothiols in human plasma and whole blood.

Isolated human neutrophilic leukocytes were stimulated to produce hydrogen peroxide (H2OZ) and to secrete cytoplasmic granule components including myeloperoxidase into the medium. Myeloperoxidase catalyzed the oxidation of chloride (C1-) by H20z to yield hypochlorous acid (HOCl), which reacted with endogenous nitrogen compounds to yield derivatives containing nitrogen-chlorine (N-Cl) bonds. Compounds available for reaction with HOCl were ammonia (NH:), taurine, a-amino acids, and granule proteins and peptides that were released into the medium. A portion of the N-Cl derivatives formed under these conditions accumulated in the extracellular medium. These long lived oxidizing agents were characterized as hydrophilic, low molecular weight, mono-N-chloramine (RNHCl) derivatives based on their absorption spectrum, ability to oxidize 5-thio-2-nitrobenzoic acid and to chlorinate ammonia (NH:), and behavior upon ultrafiltration, gel chromatography, and extraction with organic solvents. The RNHCl derivatives were of low toxicity, but reacted with N&+ to yield the lipophilic oxidizing agent monoehloramine (NH2Cl). Therefore, the addition of NH: conferred bactericidal, cytotoxic, and cytolytic activities on the RNHCl derivatives. The results indicate that taurine and other neutrophil amines protect neutrophils and other cells against oxidative attack by acting as a trap for HOCl and by competing with endogenous NH: for reaction with HOCl. However, the RNHCl derivatives act as a reserve of oxidizing equivalents that is converted to a toxic form when an increase in NH: concentration favors formation of NH2Cl.

Matthew B. Grisham

Papers

Role of the Enteric Microbiota in Intestinal Homeostasis and Inflammation

Interferon-γ and Interleukin-10 Reciprocally Regulate Endothelial Junction Integrity and Barrier Function

The Chemical Biology of Nitric Oxide

Dynamic state of S-nitrosothiols in human plasma and whole blood.

Chlorination of Endogenous Amines by Isolated Neutrophils