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: 3.52). 07/2011; 25(3):255-64. DOI: 10.1016/j.niox.2011.07.002
Source: PubMed


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.

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Available from: Sangwon F Kim
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    • "High levels of PGI 2 inhibit LPS-stimulated iNOS induction in J774.2 macrophages or murine peritoneal macrophages without affecting the enzyme once expressed (Kim, 2011). In rat Kupffer cells stimulated with endotoxin, inhibition of endogenously produced PG by indomethacin resulted in a concomitant inhibition of NO release (Kim, 2011), and conversely, indomethacin did not inhibit NO release in mouse RAW 264.7 cells nor J774.2 macrophages (Salvemini et al., 1993). Thus, there are clearly cellspecific responses to PG exposure. "
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    ABSTRACT: Nitric oxide synthase and cyclooxygenase pathways share a number of similarities. NOS produces nitric oxide (NO) and COX generates prostaglandins. Two major forms of NOS and COX have been discovered to date: constitutive versus inducible forms. The constitutive forms play a role in housekeeping and physiological states, while the inducible forms are overexpressed under pathological conditions such as inflammation in a variety of cells, producing a large amount of NO or prostaglandins. The cross talk between the COX and NOS pathways was initially reported in 1993 when they demonstrated in a series of in vitro and in vivo studies that NO activates the COX enzymes to produce increased amounts of prostaglandins. Those studies led to the concept that COX enzymes represent important endogenous "receptor" targets for amplifying or modulating the multifaceted roles of NO in physiology and pathology. 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 focuses in particular on recent advances in this field that extend our understanding of these two pathways under various systems.
    Full-text · Article · Sep 2014 · Vitamins & Hormones
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    • "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]. "
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    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.
    Full-text · Article · Aug 2014
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    • "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. "
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    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.
    Full-text · Article · Apr 2014 · Life sciences
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