Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology

2006 ◽  
Vol 291 (6) ◽  
pp. C1225-C1231 ◽  
Author(s):  
Cecilia Giulivi ◽  
Kazunobu Kato ◽  
Christopher Eric Cooper
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Oxygen Consumption ◽  
Subcellular Localization ◽  
Calcium Signaling ◽  
Intracellular Calcium ◽  
Reactive Oxygen ◽  
No Production ◽  
Oxygen Species ◽  
Signal Molecule

Mitochondrial biochemistry is complex, expanding from oxygen consumption, oxidative phosphorylation, lipid catabolism, heme biosynthesis, to apoptosis, calcium homeostasis, and production of reactive oxygen species, including nitric oxide (NO). The latter molecule is produced by a mitochondrial NO synthase (mtNOS). The rates of consumption and production determine the steady-state concentration of NO at subcellular levels, leading to regulation of mitochondrial events. Temporospatial processes tightly regulate production of NO in mitochondria to maximize target effects and minimize deleterious reactions. Temporal regulatory mechanisms of mtNOS include activation by calcium signaling and transcriptional/translational regulations. Calcium-activated mtNOS inhibits mitochondrial respiration, resulting in a decrease of the oxygen consumption. This negative regulation antagonizes the effects of calcium on calcium-dependent dehydrogenases in the citric acid cycle, preventing the formation of anoxic foci. Temporal regulation of NO production by intracellular calcium signaling is a complex process, considering the heterogeneous intracellular calcium response and distribution. NO production in mitochondria is spatially regulated by mechanisms that determine subcellular localization of mtNOS, likely acylation and protein-protein interactions, in addition to transcriptional regulation as neuronal NOS. Because NO rapidly decays in mitochondria, subcellular localization of mtNOS is crucial for NO to function as a signal molecule. These temporospatial processes are biologically important to allow NO to act as an effective signal molecule to regulate mitochondrial events such as oxygen consumption and reactive oxygen species production.

scholarly journals Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling

2000 ◽  
Vol 97 (1) ◽  
pp. 448-453 ◽  
Author(s):  
O. Yermolaieva ◽  
N. Brot ◽  
H. Weissbach ◽  
S. H. Heinemann ◽  
T. Hoshi
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Calcium Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging

2014 ◽  
Vol 306 (5) ◽  
pp. F542-F550 ◽  
Author(s):  
Kevin L. Gordish ◽  
William H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
No Production ◽  
Oxygen Species ◽  
Before And After ◽  
Basal Blood Pressure ◽  
Control Response ◽  
Renal Vascular ◽  
Endothelial Nitric Oxide

Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min−1·gram of kidney weight−1 (gkw); n = 8; P < 0.002] and decreased renal vascular resistance (RVR) by 18% from 15.00 ± 1.65 to 12.32 ± 1.20 arbitrary resistance units (ARU; P < 0.002). To test the participation of NO, we administered 5.0 mg/kg bw resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min−1·gkw−1; n = 10; P < 0.001). To test the participation of ROS, we gave 5.0 mg/kg bw resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min−1·gkw−1; n = 7; P < 0.001) and decreased RVR 19% (from 18.83 ± 1.37 to 15.27 ± 1.37 ARU). Tempol blocked resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min−1·gkw−1; n = 7; P < 0.03) and the decrease in RVR posttempol was 44% of the control response (3.56 ± 0.34 vs. 1.57 ± 0.21 ARU; n = 7; P < 0.006). We also tested the role of endothelium-derived prostanoids. Two days of 10 mg/kg bw indomethacin pretreatment did not alter basal blood pressure or RBF. Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products.

Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide

2007 ◽  
Vol 102 (4) ◽  
pp. 1687-1695 ◽  
Author(s):  
Theodoros Vassilakopoulos ◽  
Sabah N. A. Hussain
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Muscle Activation ◽  
Reactive Oxygen ◽  
Respiratory Muscles ◽  
Repair Process ◽  
No Production ◽  
Oxygen Species ◽  
Glycogen Depletion ◽  
Diaphragmatic Muscle

Strenuous diaphragmatic contractions that are induced by inspiratory resistive breathing initiate an inflammatory response that involves the elevation of pro- and anti-inflammatory cytokines within the diaphragm, which may then spill into the circulation. The production of reactive oxygen species within working respiratory muscles increases in response to these strenuous diaphragmatic contractions. At the same time, diaphragmatic nitric oxide (NO) production declines significantly, despite a time-dependent increase in NO synthase isoform protein expression. The increase in adhesion molecule expression and infiltration of granulocytes and macrophages that follows may contribute to the contraction-induced diaphragm injury. Enhanced generation of reactive oxygen species, oxidative stress augmentation, reduced NO production, and glycogen depletion are potential stimuli for the cytokine induction that is secondary to strenuous diaphragmatic contractions. This production of cytokines within the diaphragm may contribute to the diaphragmatic muscle fiber injury that occurs with strenuous contractions or to the expected repair process. TNF-α is a cytokine that compromises diaphragmatic contractility and may contribute to muscle wasting. IL-6 is a cytokine that may have beneficial systemic effects by mobilizing glucose from the liver and free fatty acids from the adipose tissue and providing them to the strenuously working respiratory muscles. Thus cytokine upregulation within the working diaphragm may be adaptive and maladaptive.

scholarly journals Anti-Inflammatory and Anti-Oxidant Effects of Epilobium amurense subsp. cephalostigma via Activation of Nrf2/HO-1 and Inhibition of NF-κB/p38 MAPK Signaling in LPS-Stimulated Macrophages

2021 ◽  
Vol 11 (24) ◽  
pp. 11715
Author(s):  
Se-Yun Cheon ◽  
Hyun-Ae Kang ◽  
Bo-Ram Jin ◽  
Hyo-Jung Kim ◽  
Yea-Jin Park ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
P38 Mapk ◽  
Reactive Oxygen ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Anti Inflammatory

The genus Epilobium consists of approximately 200 species that are distributed worldwide. Some of these herbs have been used for the treatment of diarrhea, infection, irritation, and other disorders associated with inflammation. Unlike that of other Epilobium species, there is little scientific understanding of the pharmacological effect of Epilobium amurense subsp. cephalostigma (Hausskn.) C. J. Chen, Hoch & P. H. Raven. In this study, we demonstrated the anti-inflammatory and antioxidative properties of an E. amurense 95% ethanol extract (EACEE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and observed the underlying mechanism of this effect. We measured the productions of nitric oxide (NO) and reactive oxygen species, and examined the actions of EACEE on transcription factors in the macrophages. EACEE reduced NO production and inducible nitric oxide synthase protein levels via the inhibition of the nuclear factor (NF)-κB pathway. Additionally, EACEE suppressed redundant reactive oxygen species production and regulated nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling. Furthermore, EACEE significantly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). Overall, these results indicate that EACEE exerts anti-inflammatory and antioxidant effects via the activation of Nrf2/HO-1 and inhibition of NF-κB/p38 MAPK signaling.

Benzophenone Esters and Sulfonates: Synthesis and their Potential as Antiinflammatory Agents

2019 ◽  
Vol 15 (2) ◽  
pp. 162-174
Author(s):  
Arshia ◽  
Almas Jabeen ◽  
Aisha Faheem ◽  
Khalid M. Khan ◽  
Shazia Shah ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Sulfonyl Chloride ◽  
Reactive Oxygen ◽  
No Production ◽  
Spectroscopic Techniques ◽  
Oxygen Species ◽  
Standard Drug ◽  
Synthetic Compounds ◽  
Antioxidant Defense Systems

Background: Inflammation is a biological rejoinder of vascular tissues against destructive agents e.g. irritants, damaged cell or pathogens. During inflammation, respiratory burst occurs by activated phagocytes which help to destroy invading pathogens. Phagocytic cells such as neutrophils and macrophages are one of the major sources of reactive oxygen species (ROS) and nitric oxide (NO). Normally, the redox environment is maintained by various antioxidant defense systems, however, these reactive oxygen species may be destructive and can lead to various pathological conditions. Methods: Benzophenone esters and sulfonates (1-18) were synthesized through one pot synthesis by reacting 4-hydroxy benzophenone either different benzoyl chloride or sulfonyl chloride. These synthetic compounds were evaluated for their in vitro immunosuppressive potential on two parameters of innate immune response including inhibition of intracellular reactive oxygen species (ROS) and nitric oxide (NO). ROS were induced in polymorphonuclear leukocytes (PMNs) isolated from human whole blood by serum opsonized zymosan stimulation, whereas NO were produced in J774.2 cells by lipopolysachharides (LPS) stimulation. Moreover, cytotoxicity of compounds was also determined using NIH-3T3 fibroblast cells (ATCC, Manassas, USA) was evaluated by using the standard MTT colorimetric assay. Results: All compounds inhibited the production of ROS at various extent among which compounds 2, 5, 6, 8, 10, 13 and 16 were found to be the potent inhibitors of ROS with IC50 values ranging between (1.0 - 2.2 µg/mL) as compared to ibuprofen (IC50 = 2.5 ± 0.6 µg/mL) as the standard drug. Compounds 2, 7, 11, 13, 14 and 18 showed good inhibition of NO production with % inhibition values ranging between (63.6% - 76.7%) at concentration of 25 µg/mL as compared to NG-monomethyl-Larginine (L-NMMA 65.6 ± 1.1 µg/mL) as the standard. All other derivatives showed moderate to low level of inhibition on both tested parameters. Cytotoxicity activity also showed nontoxicity of synthetic compounds. Structures of all the synthetic compounds were confirmed through 1H-NMR, 13C-NMR, EI-MS and HREI-MS spectroscopic techniques. Conclusion: Compounds 2 and 13 were found to be good dual antiinflammatory (ROS and NO) agent. However, compounds 5, 6, 8, 10 and 16 were found to be selectively active for ROS inhibitory studies. Compounds 7, 11, 14 and 18 were discriminatory active at NO inhibition assay. These initial findings of antiinflammatory activity concluded that these compounds might have the potential to develop a novel non-steroidal antiinflammatory drugs (NSAIDs), non-acidic antiinflammatory agent. Most active compounds 2, 5-8, 10, 13, 14 and 16 showed nontoxicity of synthetic compounds.

EFFECTS OF REACTIVE OXYGEN SPECIES ON INTRACELLULAR CALCIUM IN BOVINE TRACHEAL EPITHELIUM: Modulation by Nitric Oxide

2000 ◽  
Vol 26 (5) ◽  
pp. 335-348 ◽  
Author(s):  
Soichiro Kanoh ◽  
Mitsuko Kondo ◽  
Jun Tamaoki ◽  
Hideo Kobayashi ◽  
Kazuo Motoyoshi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Intracellular Calcium ◽  
Reactive Oxygen ◽  
Tracheal Epithelium ◽  
Oxygen Species

scholarly journals Virescenosides From the Holothurian-Associated Fungus Acremonium Striatisporum Kmm 4401

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 616 ◽  
Author(s):  
Zhuravleva ◽  
Antonov ◽  
Oleinikova ◽  
Khudyakova ◽  
Popov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Urease Activity ◽  
Agar Medium ◽  
Reactive Oxygen ◽  
Potassium Bromide ◽  
No Production ◽  
Spectroscopic Methods ◽  
Oxygen Species ◽  
Wort Agar

Ten new diterpene glycosides virescenosides Z9-Z18 (1–10) together with three known analogues (11–13) and aglycon of virescenoside A (14) were isolated from the marine-derived fungus Acremonium striatisporum KMM 4401. These compounds were obtained by cultivating fungus on wort agar medium with the addition of potassium bromide. Structures of the isolated metabolites were established based on spectroscopic methods. The effects of some isolated glycosides and aglycons 15–18 on urease activity and regulation of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) production in macrophages stimulated with lipopolysaccharide (LPC) were evaluated.

scholarly journals Piltunines A–F from the Marine-Derived Fungus Penicillium piltunense KMM 4668

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 647 ◽  
Author(s):  
Shamil Sh. Afiyatullov ◽  
Olesya I. Zhuravleva ◽  
Alexandr S. Antonov ◽  
Elena V. Leshchenko ◽  
Mikhail V. Pivkin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Cytotoxic Activity ◽  
Reactive Oxygen ◽  
No Production ◽  
Spectroscopic Methods ◽  
Oxygen Species ◽  
The Absolute ◽  
Nuclear Overhauser ◽  
Circular Dichroïsm

Six new carotane sesquiterpenoids piltunines A–F (1–6) together with known compounds (7–9) were isolated from the marine-derived fungus Penicillium piltunense KMM 4668. Their structures were established using spectroscopic methods. The absolute configurations of 1–7 were determined based on circular dichroism (CD) and nuclear Overhauser spectroscopy (NOESY) data as well as biogenetic considerations. The cytotoxic activity of some of the isolated compounds and their effects on regulation of reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages were examined.

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