Nitric Oxide Is Said to Be the “Miracle Molecule” That “Reverses Aging”
Robert Fried, Lynn Nezin in Evidence-Based Proactive Nutrition to Slow Cellular Aging, 2017
This chapter focuses on a curious molecule, a gas actually, nitric oxide (NO), made by the cells in the inner lining of our blood vessels, the endothelium. The cells use an enzyme, nitric oxide synthase (NOS), to derive NO from the amino acid L-arginine, a component of protein in foods in the diet. Nitric oxide (NO) is formed from L-arginine by nitric oxide synthase enzymes (NOS), there being three isoforms: eNOS forms NO in the endothelium to control blood flow in the vessels; nNOS forms NO in nerve and brain cells to effect their communication; and inducible iNOS forms NO in macrophages activated to combat inflammation. Endothelial NO formation declines more rapidly in men than in women over the lifespan; systolic blood pressure rises in men and women, and diastolic blood pressure rises into the middle years in both men and women.
Nitric Oxide and Hydrogen Peroxide Production during Apoptosis of Human Neutrophils
Luc Montagnier, Rene Olivier, Catherine Pasquier in Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases, 1998
Polymorphonuclear leukocytes (PMN) play determinant roles in immunity and inflammation. These processes are mediated by the activation of the NADPH oxidase, which generates superoxide anion (O2), and by the activation of a cytoplasmic, constitutive and inducible nitric oxide synthase (NOS and iNOS), which produces nitric oxide (NO*) (1-5). Superoxide anion, H2O2, and NO" are not only efficient antimicrobial effector molecules, they are key mediators in inflammatory reactions in which they participate, altering the expression of endothelial adhesion molecules and inducing the production of different cytokines (6-8). Together with these molecules and proteolytic enzymes, PMN cells can mediate intra-and extracellular cytotoxicity and modulate different cellular functions in adjacent cells. After degradation of the ingested material, polymorphonuclear cells die. These terminally differentiated cells are not able to proliferate and in vitro they demise rapidly by an apoptotic mechanism; PMN senecent cells are then recognized by macrophages by a cell-surface mechanism mediated by vitronectin receptor (9).
Modulation of Glutamate Release and Toxicity by Nitric Oxide
Giuseppe Poli in Free Radicals in Brain Pathophysiology, 2000
Glutamate is the major excitatory neurotransmitter in the central nervous system and, like other neurotransmitters, interacts with specific receptors that are of two major types: ionotropic receptors and metabotropic receptors (1,2). The iono tropic receptors have been classified based on their pharmacological and physio logical properties as A-methyl-D-aspartate (NMDA), kainate, and a-amino-3hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Activation of the NMDA receptors leads to influx of large quantities of Ca2+ and Na+, which nor mally serve as the physiological trigger signal leading to cell depolarization, but under overstimulation of the NMDA receptor inappropriately high concentrations of Ca2+ are reached intracellularly leading to interference with mitochondrial function and overactivation of Ca2+-dependent cellular enzymes [reviewed in Refs. 2 and 3], including nitric oxide synthase (NOS) in nerve cells containing this enzyme, which causes increased production of NO (4,5). Thus, the toxicity of glutamate is explained to a great extent in terms of the overload of Ca2+ it produces in the cell and the consequences of that overload (6).
Nitric Oxide Mediates IL-1β-Induced Islet Dysfunction and Destruction: Prevention by Dexamethasone
Published in Autoimmunity, 1993
John A. Corbett, Jin Lin Wang, Thomas P. Misko, Weiguo Zhao, William F. Hickey, Michael L. Mcdaniel
Nitric oxide has recently been implicated as a cellular effector molecule that mediates interleukin-1β (IL-lβ)-induced inhibition of glucose-stimulated insulin secretion by islets of Langerhans. In this study evidence is presented which demonstrates that islets contain both the cytokine inducible and the constitutive isoforms of nitric oxide synthase as determined by NADPH diaphorase staining and immunohistochemical localization. Untreated islets contain NADPH diaphorase activity, and the intensity of NADPH diaphorase staining is dramatically increased after culture for 18 hrs with IL-1β. Both control and IL-lβ-induced NADPH diaphorase staining of islets is inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (NMMA). Importantly, ~60–70% of islet cells stained positive for NADPH diaphorase (under both IL-1β treated and control conditions), suggesting that a subset of islet cells contain nitric oxide synthase. The β-cell appears to be the endocrine cell type which contains constitutive nitric oxide synthase as demonstrated by immunohistochemical co-localization of constitutive nitric oxide synthase and insulin. IL-1β is believed to stimulate the expression of cytokine inducible nitric oxide synthase because the synthetic glucocorticoid, dexamethasone, prevents IL-1β induced inhibition of glucose stimulated insulin secretion and cGMP accumulation by islets. Both dexamethasone, and the nitric oxide synthase inhibitors NMMA and aminoguanidine also prevent IL-1β induced islet degeneration. These results indicate that nitric oxide produced by the inducible isoform of nitric oxide synthase mediates cytokine induced islet dysfunction and destruction, and that the β-cell is the islet endocrine cellular source of constitutive nitric oxide synthase.
Potent activation of nitric oxide synthase by garlic: A basis for its therapeutic applications
Published in Current Medical Research and Opinion, 1995
Indrajit Das, Nusrat S. Khan, Suren R. Sooranna
Summary Garlic (Allium sativum L.) is thought to have a variety of therapeutic applications including inhibition of platelet aggregation. Many of the therapeutic actions of garlic parallel the physiological effects of nitric oxide and may be explained by its ability to increase nitric oxide synthase activity intracellularly. Our studies showed that both water and alcoholic extracts of garlic are very potent inhibitors of platelet aggregation induced by epinephrine and ADP. Similar dilutions of garlic extract also activated nitric oxide synthase activity in isolated platelets in vitro. The same extract was also very effective in activating nitric oxide synthase activity in placental villous tissue. The addition of garlic extracts increased nitric oxide synthase activity in a dose-dependent manner. Nitrite levels in the supernatants of incubated placental villous tissue were similarly increased. Activation of calcium-dependent nitric oxide synthase and the subsequent production of nitric oxide is probably the most novel mechanism yet claimed by which garlic can exert its therapeutic properties.
Applications for regulatory region of nitric oxide synthase isoforms
Published in Expert Opinion on Therapeutic Patents, 1998
This patent application focuses on new regulatory sites found in the flavin mononucleotide (FMN) binding domain of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS), the two constitutive nitric oxide synthases (cNOS). The new regulatory sites differ on the two enzymes. The inducible nitric oxide synthase (iNOS) lacks this extra polypeptide insert. It is alleged that this insert acts as an autoinhibitory control by limiting calcium-calmodulin (CaM) binding to the enzyme.