scholarly journals Carbon Monoxide, a Novel Neural Messenger, Does Not Modulate Extracellular Glutamate Concentration in Forebrain Ischemia

1996 ◽  
Vol 16 (5) ◽  
pp. 1075-1078 ◽  
Author(s):  
Shunya Takizawa ◽  
Hitoshi Fujita ◽  
Saori Ogawa ◽  
Yukito Shinohara
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Protoporphyrin Ix ◽  
Zinc Protoporphyrin ◽  
Forebrain Ischemia ◽  
Extracellular Glutamate ◽  
Glutamate Concentration ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

We investigated the role of carbon monoxide as a neural modulator of extracellular glutamate concentration in rat hippocampus CA1 in transient forebrain ischemia by using metalloporphyrins, which block the production of carbon monoxide through the inhibition of heme oxygenase (HO) activity. Infusion of 10 and 100 μ M zinc protoporphyrin IX, which inhibits nitric oxide synthase activity as well as HO activity, significantly increased glutamate concentration compared with that on the vehicle-treated side. However, infusion of 100 μ M tin mesoporphyrin IX, which inhibits only HO activity, did not affect glutamate concentration in ischemia. Our results therefore do not support the hypothesis that carbon monoxide acts as a neural messenger through the modulation of extracellular glutamate concentration in ischemia.

scholarly journals eNOS activation and NO function: Structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity

2011 ◽  
Vol 210 (3) ◽  
pp. 271-284 ◽  
Author(s):  
Ruslan Rafikov ◽  
Fabio V Fonseca ◽  
Sanjiv Kumar ◽  
Daniel Pardo ◽  
Charles Darragh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Posttranslational Modifications ◽  
Endothelial Nitric Oxide Synthase ◽  
Regulatory Region ◽  
Enos Uncoupling ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Nitric Oxide Synthase Activity

Rather than being a constitutive enzyme as was first suggested, endothelial nitric oxide synthase (eNOS) is dynamically regulated at the transcriptional, posttranscriptional, and posttranslational levels. This review will focus on how changes in eNOS function are conferred by various posttranslational modifications. The latest knowledge regarding eNOS targeting to the plasma membrane will be discussed as the role of protein phosphorylation as a modulator of catalytic activity. Furthermore, new data are presented that provide novel insights into how disruption of the eNOS dimer prevents eNOS uncoupling and the production of superoxide under conditions of elevated oxidative stress and identifies a novel regulatory region we have termed the ‘flexible arm’.

scholarly journals Inhibition of MEK/ERK1/2 signalling alters endothelial nitric oxide synthase activity in an agonist-dependent manner

2006 ◽  
Vol 398 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Jacqueline M. Cale ◽  
Ian M. Bird
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Intracellular Trafficking ◽  
Enos Activity ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Nitric Oxide Synthase Activity

eNOS (endothelial nitric oxide synthase) activity is post-translationally regulated in a complex fashion by acylation, protein–protein interactions, intracellular trafficking and phosphorylation, among others. Signalling pathways that regulate eNOS activity include phosphoinositide 3-kinase/Akt, cyclic nucleotide-dependent kinases [PKA (protein kinase A) and PKG], PKC, as well as ERKs (extracellular-signal-regulated kinases). The role of ERKs in eNOS activation remains controversial. In the present study, we have examined the role of ERK1/2 in eNOS activation in HUVEC-CS [transformed HUVEC (human umbilical-vein endothelial cells)] as well as a widely used model for eNOS study, transiently transfected COS-7 cells. U0126 pretreatment of HUVEC-CS potentiated ATP-stimulated eNOS activity, independent of changes in intracellular Ca2+ concentration ([Ca2+]i). In COS-7 cells transiently expressing ovine eNOS, U0126 potentiated A23187-stimulated eNOS activity, but inhibited ATP-stimulated activity. Compensatory changes in phosphorylation of five key eNOS residues did not account for changes in A23187-stimulated activity. However, in the case of ATP, altered phosphorylation and changes in [Ca2+]i may partially contribute to U0126 inhibition of activity. Finally, seven eNOS alanine mutants of putative ERK1/2 targets were generated and the effects of U0126 pretreatment on eNOS activity were gauged with A23187 and ATP treatment. T97A-eNOS was the only construct significantly different from wild-type after U0126 pretreatment and ATP stimulation of eNOS activation. In the present study, eNOS activity was either potentiated or inhibited in COS-7 cells, suggesting agonist dependence for MEK/ERK1/2 signalling [where MEK is MAPK (mitogen-activated protein kinase)/ERK kinase] to eNOS and a complex mechanism including [Ca2+]i, phosphorylation and, possibly, intracellular trafficking.

scholarly journals Role of heme oxygenase-2 in pial arteriolar response to acetylcholine in mice with and without transfusion of cell-free hemoglobin polymers

2008 ◽  
Vol 295 (2) ◽  
pp. R498-R504 ◽  
Author(s):  
Xinyue Qin ◽  
Herman Kwansa ◽  
Enrico Bucci ◽  
Sylvain Doré ◽  
Darren Boehning ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Oxygen Carrier ◽  
Protoporphyrin Ix ◽  
Cranial Window ◽  
Dilatory Response ◽  
A Cell ◽  
Oxide Synthase

Carbon monoxide derived from heme oxygenase (HO) may participate in cerebrovascular regulation under specific circumstances. Previous work has shown that HO contributes to feline pial arteriolar dilation to acetylcholine after transfusion of a cell-free polymeric hemoglobin oxygen carrier. The role of constitutive HO2 in the pial arteriolar dilatory response to acetylcholine was determined by using 1) HO2-null mice (HO2−/−), 2) the HO inhibitor tin protoporphyrin IX (SnPPIX), and 3) 4,5,6,7-tetrabromobenzotriazole (TBB), an inhibitor of casein kinase-2 (CK2)-dependent phosphorylation of HO2. In anesthetized mice, superfusion of a cranial window with SnPPIX decreased arteriolar dilation produced by 10 μM acetylcholine by 51%. After partial polymeric hemoglobin exchange transfusion, the acetylcholine response was normal but was reduced 72% by SnPPIX and 95% by TBB. In HO2−/− mice, the acetylcholine response was modestly reduced by 14% compared with control mice and was unaffected by SnPPIX. After hemoglobin transfusion in HO2−/− mice, acetylcholine responses were also unaffected by SnPPIX and TBB. In contrast, nitric oxide synthase inhibition completely blocked the acetylcholine responses in hemoglobin-transfused HO2−/− mice. We conclude 1) that HO2 activity partially contributes to acetylcholine-induced pial arteriolar dilation in mice, 2) that this contribution is augmented in the presence of a plasma-based hemoglobin polymer and appears to depend on a CK2 kinase mechanism, 3) that nitric oxide synthase activity rather than HO1 activity contributes to the acetylcholine reactivity in HO2−/− mice, and 4) that plasma-based polymeric hemoglobin does not scavenge all of the nitric oxide generated by cerebrovascular acetylcholine stimulation.

Role of dietary fish oil on nitric oxide synthase activity and oxidative status in mice red blood cells

2014 ◽  
Vol 5 (12) ◽  
pp. 3208-3215 ◽  
Author(s):  
Marcela A. Martins ◽  
Monique B. Moss ◽  
Iara K. S. Mendes ◽  
Márcia B. Águila ◽  
Carlos Alberto Mandarim-de-Lacerda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Acids ◽  
Nitric Oxide Synthase ◽  
Fish Oil ◽  
Blood Cells ◽  
Oxidative Status ◽  
Dietary Fish ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

The consumption of n-3 polyunsaturated fatty acids derived from fish oil is associated with cardiovascular benefits, which may result from the participation of nitric oxide.

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