Article

The role of nitric oxide in prostaglandin biology; Update

Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, 125 S, 31st St. TRL Rm 2207, Philadelphia, PA 19104, USA.
Nitric Oxide (Impact Factor: 3.18). 07/2011; 25(3):255-64. DOI: 10.1016/j.niox.2011.07.002
Source: PubMed

ABSTRACT The biosynthesis of nitric oxide (NO) and prostaglandin share many similarities. Two major forms of nitric oxide synthase (NOS) and cyclooxygenase (COX) have been identified: constitutive versus inducible. In general, the constitutive form functions in housekeeping and physiologic roles whereas the inducible form is up-regulated by mitogenic or inflammatory stimuli and is responsible for pathophysiological responses. The cross talk between the COX and NOS pathways was initially reported in 1993 and since then, numerous studies have been undertaken to delineate the functional consequences of this interaction as well as the potential mechanism by which each pathway interacts. This review will focus in particular on recent advances in this field that extend our understanding of these two pathways under various systems.

Download full-text

Full-text

Available from: Sangwon F Kim, Sep 01, 2015
0 Followers
 · 
93 Views
 · 
72 Downloads
  • Source
    • "The sGC-cGMP signaling is one of the major pathways of NO-related vascular function mediation [106]. NO-associated COX activation is of importance in the regulation of a pro-inflammatory process [79,107]. Additionally, at low NO concentrations it modulates the redox form of COX, converting the ferrous iron to the ferric active form, acting also as a scavenger of superoxide [61]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The endothelium performs a crucial role in maintaining vascular integrity leading to whole organ metabolic homeostasis. Endothelial dysfunction represents a key etiological factor leading to moderate to severe vasculopathies observed in both Type 2 diabetic and Alzheimer's Disease (AD) patients. Accordingly, evidence-based epidemiological factors support a compelling hypothesis stating that metabolic rundown encountered in Type 2 diabetes engenders severe cerebral vascular insufficiencies that are causally linked to long term neural degenerative processes in AD. Of mechanistic importance, Type 2 diabetes engenders an immunologically mediated chronic pro-inflammatory state involving interactive deleterious effects of leukocyte-derived cytokines and endothelial-derived chemotactic agents leading to vascular and whole organ dysfunction. The long term negative consequences of vascular pro-inflammatory processes on the integrity of CNS basal forebrain neuronal populations mediating complex cognitive functions establish a striking temporal comorbidity of AD with Type 2 diabetes. Extensive biomedical evidence supports the pivotal multi-functional role of constitutive nitric oxide (NO) production and release as a critical vasodilatory, anti-inflammatory, and anti-oxidant, mechanism within the vascular endothelium. Within this context, we currently review the functional contributions of dysregulated endothelial NO expression to the etiology and persistence of Type 2 diabetes-related and co morbid AD-related vasculopathies. Additionally, we provide up-to-date perspectives on critical areas of AD research with special reference to common NO-related etiological factors linking Type 2 diabetes to the pathogenesis of AD.
    08/2014; 20:118-29. DOI:10.12659/MSMBR.891278
  • Source
    • "Actually, in the present study, central pretreatment with 7-nitroindazole abolished bombesin-induced Fos expression in FG-labeled PVN neurons containing COX-1 in the rat, suggesting a possibility that NO produced by nNOS might activate COX-1 in the spinally projecting PVN neurons in response to bombesin in vivo. NO-mediated activation of COX seems to be induced at least by S-nitrosylation of COX protein in vitro (Kim, 2011). We recently reported that central pretreatment with thiol-reducing and -alkylating regents, blocking of protein S-nitrosylation, attenuated i.c.v. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims Cyclooxygenase (COX) can be activated by nitric oxide-induced (NO-induced) conversion of cysteine thiol group of COX into S-nitrosothiol. We previously reported the involvement of brain COX/NO synthase (NOS) in centrally administered bombesin-, a stress-related neuropeptide, induced secretion of rat adrenal noradrenaline and adrenaline. To examine a possible involvement of the NO-induced modification of COX in bombesin-induced response, we investigated whether bombesin induces close proximity of COX-1 and neuronal NOS (nNOS) or S-nitroso-cysteine in pre-sympathetic spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN), a regulatory center of adrenomedullary outflow. Main methods In twelve-week-old male Wistar rats, pre-sympathetic spinally projecting neurons in the PVN were labeled with a retrograde tracer Fluoro-Gold (FG). After intracerebroventricular administration of bombesin, we performed double immunohistochemical analysis for Fos and COX-1 or nNOS in FG-labeled PVN neurons. We also performed a fluorescent in situ proximity ligation assay (PLA) for visualizing of close proximity (> 40 nm) of COX-1 with nNOS or S-nitroso-cysteine. Key findings Bombesin significantly increased the number of Fos-immunoreactive cells in FG-labeled PVN neurons with COX-1 or nNOS immunoreactivity. 7-Nitroindazole, a selective nNOS inhibitor, abolished Fos-immunoreactivity induced by bombesin in COX-1-immunoreactive FG-labeled PVN neurons. Bombesin also induced PLA-positive signals indicating close proximity of COX-1/nNOS and COX-1/S-nitroso-cysteine in FG-labeled PVN neurons. Significance Centrally administered bombesin possibly induces S-nitrosylation of COX-1 through close proximity of COX-1 and nNOS in pre-sympathetic spinally projecting PVN neurons, thereby activating COX-1 during the bombesin-induced activation of central adrenomedullary outflow in the rat.
    Life sciences 04/2014; 100(2). DOI:10.1016/j.lfs.2014.01.079 · 2.30 Impact Factor
  • Source
    • "The ramifications between NOS and COX pathways have been frequently investigated in the past (reviewed in [4]), but results are inconsistent. For instance, in murine macrophages, paracetamol, at pharmacologically relevant plasma concentrations (60–120 í µí¼‡M), has been reported not to affect iNOS activity [17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1 α , respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2 α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans.
    Oxidative Medicine and Cellular Longevity 03/2014; 2014:212576. DOI:10.1155/2014/212576 · 3.36 Impact Factor
Show more