Nitric oxide, peroxynitrite, S-nitrosothiols and thiols are unlikely to exert their effects on recombinant cyclooxygenase-1 and cyclooxygenase-2 activity in vitro by modifying cysteine moieties

Nitric Oxide ◽  
2012 ◽  
Vol 26 (3) ◽  
pp. 192-194 ◽  
Author(s):  
Dimitrios Tsikas ◽  
Jonas Niemann
Keyword(s):  
Nitric Oxide ◽  
Cyclooxygenase 2 ◽  
Cyclooxygenase 1 ◽  
Recombinant Cyclooxygenase 1

scholarly journals gem-Difluorobisarylic derivatives: design, synthesis and anti-inflammatory effect

BMC Chemistry ◽  
2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Abeer J. Ayoub ◽  
Layal Hariss ◽  
Nehme El-Hachem ◽  
Ghewa A. El-Achkar ◽  
Sandra E. Ghayad ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Protein Expression ◽  
Interleukin 6 ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Diaryl Ethers ◽  
Cyclooxygenase 1 ◽  
Anti Inflammatory ◽  
Oxide Synthase

Abstract Introduction New fluorinated diaryl ethers and bisarylic ketones were designed and evaluated for their anti-inflammatory effects in primary macrophages. Methods The synthesis of the designed molecules started from easily accessible and versatile gem-difluoro propargylic derivatives. The desired aromatic systems were obtained using Diels–Alder/aromatization sequences and this was followed by Pd-catalyzed coupling reactions and, when required, final functionalization steps. Both direct inhibitory effects on cyclooxygenase-1 or -2 activities, protein expression of cyclooxygenase-2 and nitric oxide synthase-II and the production of prostaglandin E2, the pro-inflammatory nitric oxide and interleukin-6 were evaluated in primary murine bone marrow-derived macrophages in response to lipopolysaccharide. Docking of the designed molecules in cyclooxygenase-1 or -2 was performed. Results Only fluorinated compounds exerted anti-inflammatory activities by lowering the secretion of interleukin-6, nitric oxide, and prostaglandin E2, and decreasing the protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in mouse primary macrophages exposed to lipopolysaccharide, as well as cyclooxygenase activity for some inhibitors with different efficiencies depending on the R-groups. Docking observation suggested an inhibitory role of cyclooxygenase-1 or -2 for compounds A3, A4 and A5 in addition to their capacity to inhibit nitrite, interleukin-6, and nitric oxide synthase-II and cyclooxygenase-2 expression. Conclusion The new fluorinated diaryl ethers and bisarylic ketones have anti-inflammatory effects in macrophages. These fluorinated compounds have improved potential anti-inflammatory properties due to the fluorine residues in the bioactive molecules.

Transient Up-regulation of Spinal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase following Surgical Inflammation

2003 ◽  
Vol 98 (1) ◽  
pp. 170-180 ◽  
Author(s):  
Sharron Dolan ◽  
James G. Kelly ◽  
Marie Huan ◽  
Andrea M. Nolan
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Cyclooxygenase 2 ◽  
Lumbar Spinal Cord ◽  
Chain Reaction ◽  
Cyclooxygenase 1 ◽  
Polymerase Chain ◽  
Neuronal Nos ◽  
Lumbar Spinal ◽  
Oxide Synthase

Background Surgery induces pain and hyperalgesia postoperatively. The products of cyclooxygenases and nitric oxide synthase (NOS) have been implicated in the development of inflammatory pain and hyperalgesia experimentally, and the use of drugs clinically that modify cyclooxygenase activity has been advocated in the management of perioperative pain. However, regulation of these enzymes following surgery has not been studied. Methods Adult female sheep (n = 12) undergoing a midline laparotomy for collection of ova were used in this study. Lumbar and cervical spinal cord tissue was collected from animals euthanized 1 day and 6 or 7 days after surgery and processed for cyclooxygenase (cyclooxygenase-1 and cyclooxygenase-2), neuronal NOS mRNA expression using reverse-transcription polymerase chain reaction and hybridization. Tissues were also processed for NADPH-diaphorase staining and cyclooxygenase-1 and cyclooxygenase-2 protein expression by immunohistochemistry and Western blotting. Results No alteration in cyclooxygenase-1 or cyclooxygenase-2 mRNA or protein concentrations were detected in spinal cord by reverse-transcription polymerase chain reaction and Western blotting, respectively, at 1 day or 6 or 7 days after surgery. However, using techniques that localize mRNA and protein expression ( hybridization and immunohistochemistry, respectively), increases in cyclooxygenase-2 were identified in lamina V dorsal horn neurons in lumbar spinal cord 1 day after surgery. A significant increase in neuronal NOS mRNA was observed in lumbar spinal cord 1 day after surgery, localized to laminae I-II and lamina V neurons, which returned to baseline concentrations by 6 to 7 days. NADPH-diaphorase staining was significantly increased in laminae I-II in lumbar spinal cord 1 day after surgery but not after 6 to 7 days. Conclusions Spinal cyclooxygenase and neuronal NOS pathways are differentially altered following surgical inflammation. The early and transient nature of these changes suggests that these enzymes are implicated in postoperative pain and hypersensitivity.

In vivo aspirin supplementation inhibits nitric oxide consumption by human platelets

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2737-2743 ◽  
Author(s):  
P. Claire Williams ◽  
Marcus J. Coffey ◽  
Barbara Coles ◽  
Stephanie Sanchez ◽  
Jason D. Morrow ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Platelets ◽  
Controlled Study ◽  
Double Blind ◽  
Beneficial Effects ◽  
Cyclooxygenase 1 ◽  
No Consumption ◽  
Cox 1

AbstractAntiplatelet therapies improve endothelial function in atherosclerosis, suggesting that platelets regulate vascular nitric oxide (NO) bioactivity in vivo. Herein, washed platelets consumed NO on activation in an aspirin-sensitive manner, and aspirin enhanced platelet NO responses in vitro. To examine whether in vivo aspirin can inhibit platelet NO consumption, a double-blind placebo-controlled study was conducted. After a 2-week nonsteroidal anti-inflammatory drug (NSAID)–free period, healthy men were randomly assigned and administered aspirin (75 mg/d orally) or identical placebo for 14 days, then crossed over to the opposite arm. Following in vivo aspirin, NO consumption by platelets was inhibited 91%. Rate of onset and recovery following aspirin withdrawal was consistent with cyclooxygenase 1 (COX-1) inhibition. In a small substudy, NO consumption by platelets from postmenopausal women was faster in hypercholesterolemics and less sensitive to aspirin (ie, 39% versus 76% inhibition for hypercholesterolemics or normocholesterolemics, respectively). However, 150 mg aspirin/day increased inhibition of NO consumption by platelets of hypercholesterolemics to 80%. Comparisons of platelet COX-1 or -2 expression and urinary 11-dehydro-thromboxane B2 excretion suggested that aspirin was less able to block platelet activation in vivo in hypercholesterolemia. In conclusion, aspirin inhibits NO consumption by platelets from healthy subjects, but its beneficial effects on NO bioactivity may be compromised in some hypercholesterolemic patients.

Kinetic basis for the activation of human cyclooxygenase-2 rather than cyclooxygenase-1 by nitric oxide

2018 ◽  
Vol 16 (5) ◽  
pp. 765-770 ◽  
Author(s):  
Jie Qiao ◽  
Lixin Ma ◽  
Justine Roth ◽  
Yamin Li ◽  
Yi Liu
Keyword(s):  
Nitric Oxide ◽  
Cyclooxygenase 2 ◽  
Cyclooxygenase 1

Kinetic basis for the activation of human cyclooxygenase-2 by nitric oxide.

scholarly journals In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)

2012 ◽  
Vol 44 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Nunung Yuniarti ◽  
Perdana Adhi Nugroho ◽  
Aditya Asyhar ◽  
Sardjiman Sardjiman ◽  
Zullies Ikawati ◽  
...  
Keyword(s):  
In Silico ◽  
Cyclooxygenase 2 ◽  
Cyclooxygenase 1 ◽  
In Silico Studies ◽  
Dual Inhibitors ◽  
Cox 2 ◽  
Cox 1

Interferon-α inhibits cyclooxygenase-1 and stimulates cyclooxygenase-2 expression in bladder cancer cells in vitro

2001 ◽  
Vol 29 (1) ◽  
pp. 20-24 ◽  
Author(s):  
Peter J. Boström ◽  
Pekka Uotila ◽  
Pertti Rajala ◽  
Martti Nurmi ◽  
Ilpo Huhtaniemi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cyclooxygenase 2 ◽  
Interferon Α ◽  
Cyclooxygenase 1 ◽  
Bladder Cancer Cells
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