       Document 0177
 DOCN  M9630177
 TI    [Does nitric oxide stress exist?]
 DT    9603
 AU    Torreilles J; Guerin MC; INSERM U58, Montpellier.
 SO    C R Seances Soc Biol Fil. 1995;189(3):389-400. Unique Identifier :
       AIDSLINE MED/96098961
 AB    Ten years ago, the term oxidative stress (sigma -O2) was created to
       define oxidative damage inflicted to the organism. This definition
       brings together processes involving reactive oxygen species production
       and action such as free radical production during univalent reduction of
       oxygen within mitochondria, activation of NADPH-dependent oxidase system
       on the membrane surface of neutrophils, flavoprotein-catalyzed redox
       cycling of xenobiotics and exposure to chemical and physical agents in
       the environment. Since the discovery of the nitric oxide biosynthetic
       pathway, the deleterious effects of uncontrolled nitric oxide generation
       are generally classified as oxidative stress. Indeed, products of the
       reaction of NO and superoxide lead to oxidants such as peroxinitrite,
       nitrogen dioxide and hydroxyl radical, which are involved in mechanisms
       of cell-mediated immune reactions and defence of the intracellular
       environment against microbiol invasion. However NO can also regulate
       many biological reactions and signal transduction pathways that lead to
       a variety of physiological responses such as blood pressure,
       neurotransmission, platelet aggregation, endothelin generation or smooth
       muscle cell proliferation. Then the uncontrolled NO production can lead
       to a variety of physiological and pathophysiological responses similar
       to a Nitric Oxide Stress: activation of guanylate cyclase and production
       of cGMP: overstimulation of the inducible L-arginine to L-citrulline and
       NO pathway by bactericidal endotoxins and cytokines has been shown to
       promote undesired increases in vasodilatation, which may account for
       hypotension in septic shock and cytokine therapy. stimulation of
       auto-ADP-ribosylation and modification of SH-groups of
       glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent
       mechanism: by this way, NO in excess can strongly inhibits this
       important glycolytic enzyme and reduce the cellular energy production.
       inhibition of ribonucleotide reductase: extensive inhibition of this key
       enzyme in DNA synthesis in the presence of large amounts of NO could
       lead to important antiproliferative effects; inhibition of cytochrome
       P450-dependent metabolism: in Kupffer cells and hepatocytes, LPS-induced
       overproduction of NO has been shown to inhibit cytochrome P450-dependent
       metabolism and to mediate the suppression of hepatic metabolism.
       Moreover, NO synthetized in the peripheral nervous system is known to
       mediate nonadrenergic noncholinergic (NANC) neurotransmission.
       Overstimulation of NO synthases might therefore contribute to
       pathophysiological states such as: gastrointestinal motility, reflux
       oesophagitis, asthma, adult respiratory distress syndrome (ARDS) and
       chronic pulmonary artery hypertension. To these NO-mediated biological
       functions, one could add the biological effects of NO-derivatives such
       as N-nitrosocompounds, which act as carcinogenic agents, or
       C-nitrosocompound which were recently used as zinc-ejecting agents to
       inhibit HIV-1 infectivity of human T-lymphocytes.(ABSTRACT TRUNCATED AT
       400 WORDS)
 DE    English Abstract  Free Radicals/METABOLISM  Hemeproteins/METABOLISM  In
       Vitro  Nitric Oxide/*METABOLISM  Oxidation-Reduction  *Oxidative Stress
       JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

