The role of methylene in prompt NO formation

2009 ◽  
Vol 32 (1) ◽  
pp. 343-350 ◽  
Author(s):  
Bradley A. Williams ◽  
Jeffrey A. Sutton ◽  
James W. Fleming
Keyword(s):  
2016 ◽  
Vol 12 ◽  
pp. 2588-2601 ◽  
Author(s):  
Vladimir A Stepchenko ◽  
Anatoly I Miroshnikov ◽  
Frank Seela ◽  
Igor A Mikhailopulo

The trans-2-deoxyribosylation of 4-thiouracil (4SUra) and 2-thiouracil (2SUra), as well as 6-azauracil, 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases. 4SUra revealed satisfactory substrate activity for UP and, unexpectedly, complete inertness for TP; no formation of 2’-deoxy-2-thiouridine (2SUd) was observed under analogous reaction conditions in the presence of UP and TP. On the contrary, 2SU, 2SUd, 4STd and 2STd are good substrates for both UP and TP; moreover, 2SU, 4STd and 2’-deoxy-5-azacytidine (Decitabine) are substrates for PNP and the phosphorolysis of the latter is reversible. Condensation of 2SUra and 5-azacytosine with dRib-1P (Ba salt) catalyzed by the accordant UP and PNP in Tris∙HCl buffer gave 2SUd and 2’-deoxy-5-azacytidine in 27% and 15% yields, respectively. 6-Azauracil and 6-azathymine showed good substrate properties for both TP and UP, whereas only TP recognizes 2-thio-6-azathymine as a substrate. 5-Phenyl and 5-tert-butyl derivatives of 6-azauracil and its 2-thioxo derivative were tested as substrates for UP and TP, and only 5-phenyl- and 5-tert-butyl-6-azauracils displayed very low substrate activity. The role of structural peculiarities and electronic properties in the substrate recognition by E. coli nucleoside phosphorylases is discussed.


2022 ◽  
Vol 237 ◽  
pp. 111883
Author(s):  
Shuang Yue ◽  
Chunbo Wang ◽  
Ziyang Xu ◽  
Dong Wang ◽  
Fei Zheng ◽  
...  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Takeshi Ninchoji ◽  
Dominic T Love ◽  
Ross O Smith ◽  
Marie Hedlund ◽  
Dietmar Vestweber ◽  
...  

Background:Hypoxia and consequent production of vascular endothelial growth factor A (VEGFA) promote blood vessel leakiness and edema in ocular diseases. Anti-VEGFA therapeutics may aggravate hypoxia; therefore, therapy development is needed.Methods:Oxygen-induced retinopathy was used as a model to test the role of nitric oxide (NO) in pathological neovascularization and vessel permeability. Suppression of NO formation was achieved chemically using L-NMMA, or genetically, in endothelial NO synthase serine to alanine (S1176A) mutant mice.Results:Suppression of NO formation resulted in reduced retinal neoangiogenesis. Remaining vascular tufts exhibited reduced vascular leakage through stabilized endothelial adherens junctions, manifested as reduced phosphorylation of vascular endothelial (VE)-cadherin Y685 in a c-Src-dependent manner. Treatment with a single dose of L-NMMA in established retinopathy restored the vascular barrier and prevented leakage.Conclusions:We conclude that NO destabilizes adheren junctions, resulting in vascular hyperpermeability, by converging with the VEGFA/VEGFR2/c-Src/VE-cadherin pathway.Funding:This study was supported by the Swedish Cancer foundation (19 0119 Pj ), the Swedish Research Council (2020-01349), the Knut and Alice Wallenberg foundation (KAW 2020.0057) and a Fondation Leducq Transatlantic Network of Excellence Grant in Neurovascular Disease (17 CVD 03). KAW also supported LCW with a Wallenberg Scholar grant (2015.0275). WCS was supported by Grants R35 HL139945, P01 HL1070205, AHA MERIT Award. DV was supported by grants from the Deutsche Forschungsgemeinschaft, SFB1450, B03, and CRU342, P2.


Fuel ◽  
2017 ◽  
Vol 190 ◽  
pp. 274-280 ◽  
Author(s):  
Oskar Karlström ◽  
Magnus Perander ◽  
Nikolai DeMartini ◽  
Anders Brink ◽  
Mikko Hupa
Keyword(s):  

Author(s):  
Oskar Karlström ◽  
Daniel Schmid ◽  
Mikko Hupa ◽  
Anders Brink

2003 ◽  
Vol 32 (11) ◽  
pp. 998-999 ◽  
Author(s):  
Hiroto Takahashi ◽  
Yuko Sato ◽  
Magoli Moreau ◽  
Marie-Agnes Sari ◽  
Jean-Luc Boucher ◽  
...  

2011 ◽  
Vol 158 (4) ◽  
pp. 774-789 ◽  
Author(s):  
Stephen J. Klippenstein ◽  
Lawrence B. Harding ◽  
Peter Glarborg ◽  
James A. Miller
Keyword(s):  

2004 ◽  
Vol 67 (6) ◽  
pp. 1203-1214 ◽  
Author(s):  
Karel Chalupsky ◽  
Irina Lobysheva ◽  
Françoise Nepveu ◽  
Irina Gadea ◽  
Petra Beranova ◽  
...  

1993 ◽  
Vol 265 (6) ◽  
pp. H1864-H1868 ◽  
Author(s):  
I. T. Lippe ◽  
W. Sametz ◽  
K. Sabin ◽  
P. Holzer

Capsaicin-sensitive afferent neurons control blood flow via release of peptide transmitters and formation of nitric oxide (NO). The present study examined whether capsaicin-sensitive afferent neurons and NO interact in the control of hemostasis. Afferent nerve ablation by pretreating rats with a neurotoxic dose of capsaicin (125 mg/kg) led to a 26% reduction of the time of bleeding from punctured small mesenteric arteries in pentobarbital-anesthetized animals. Blockade of NO formation by NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) attenuated the bleeding time in capsaicin-pretreated rats but had no effect in vehicle-pretreated rats. Platelet aggregation induced by ADP was significantly augmented by 12% in capsaicin-pretreated rats. L-NAME did not alter platelet aggregation in vehicle-pretreated rats but enhanced it in capsaicin-pretreated animals. The prothrombin and partial thromboplastin time and the plasma levels of fibrinogen and antithrombin III remained unchanged by capsaicin or L-NAME, whereas the thrombin time was reduced in capsaicin-pretreated rats. These data indicate that capsaicin-sensitive afferent neurons play an inhibitory role in platelet aggregation and hemostasis, a function in which they interact with the NO system.


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