Nitroxyl (HNO) signaling

Fukuto, Jon M.; Bianco, Christopher L.; Chavez, Tyler A.

doi:10.1016/j.freeradbiomed.2009.06.014

Cited by 49 publications

(50 citation statements)

References 72 publications

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“…Importantly, nitroxyl exhibits different chemical and pharmacological properties compared to NO [17–19] and reactive oxygen and other nitrogen species [20]. Although nitroxyl and NO are different chemical entities, they nonetheless, can activate similar signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

The nitroxyl donor, Angeli’s salt, reduces chronic constriction injury-induced neuropathic pain

Longhi-Balbinot

Rossaneis

Pinho‐Ribeiro

et al. 2016

Chemico-Biological Interactions

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Chronic pain is a major health problem worldwide. We have recently demonstrated the analgesic effect of the nitroxyl donor, Angeli’s salt (AS) in models of inflammatory pain. In the present study, the acute and chronic analgesic effects of AS was investigated in chronic constriction injury of the sciatic nerve (CCI)-induced neuropathic pain in mice. Acute (7th day after CCI) AS treatment (1 and 3 mg/kg; s.c.) reduced CCI-induced mechanical, but not thermal hyperalgesia. The acute analgesic effect of AS was prevented by treatment with 1H-[1,2, 4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor), KT5823 (an inhibitor of protein kinase G [PKG]) or glibenclamide (GLB, an ATP-sensitive potassium channel blocker). Chronic (7–14 days after CCI) treatment with AS (3 mg/kg, s.c.) promoted a sustained reduction of CCI-induced mechanical and thermal hyperalgesia. Acute AS treatment reduced CCI-induced spinal cord allograft inflammatory factor 1 (known as Iba-1), interleukin-1β (IL-1β), and ST2 receptor mRNA expression. Chronic AS treatment reduced CCI-induced spinal cord glial fibrillary acidic protein (GFAP), Iba-1, IL-1β, tumor necrosis factor-α (TNF-α), interleukin-33 (IL-33) and ST2 mRNA expression. Chronic treatment with AS (3 mg/kg, s.c.) did not alter aspartate aminotransferase, alanine aminotransferase, urea or creatinine plasma levels. Together, these results suggest that the acute analgesic effect of AS depends on activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. Moreover, chronic AS diminishes CCI-induced mechanical and thermal hyperalgesia by reducing the activation of spinal cord microglia and astrocytes, decreasing TNF-α, IL-1β and IL-33 cytokines expression. This spinal cord immune modulation was more prominent in the chronic treatment with AS. Thus, nitroxyl limits CCI-induced neuropathic pain by reducing spinal cord glial cells activation.

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Section: Introductionmentioning

confidence: 99%

The nitroxyl donor, Angeli’s salt, reduces chronic constriction injury-induced neuropathic pain

Longhi-Balbinot

Rossaneis

Pinho‐Ribeiro

et al. 2016

Chemico-Biological Interactions

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“…[3,4] Other biological activities of HNO include its ability to inhibit platelet aggregation, [5] to block tumor growth through inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and to act as an anti-oxidant. [6,7] Nitroxyl enhances myocardial contractility and relaxation, properties that have led to clinical trials of HNO-donating drugs for congestive heart failure. [8,9,10] Nitroxyl reacts with thiols to give an N -hydroxysulfenamide intermediate that can further react with excess thiol to give the corresponding disulfide and hydroxylamine or rearranges to a sulfinamide.…”

Section: Introductionmentioning

confidence: 99%

New acyloxy nitroso compounds with improved water solubility and nitroxyl (HNO) release kinetics and inhibitors of platelet aggregation

Mohamed¹,

Abdel‐Aziz²,

Abuo‐Rahma³

et al. 2015

Bioorganic & Medicinal Chemistry

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New acyloxy nitroso compounds, 4-nitrosotetrahydro-2H-pyran-4-yl 2,2,2-trichloroacetate and 4-nitrosotetrahydro-2H-pyran-4-yl 2,2-dichloropropanoate were prepared. These compounds release HNO under neutral conditions with half-lives between 50 and 120 minutes, identifying these HNO donors as kinetically intermediate to the much slower acetate derivative and the faster trifluoroacetic acid derivative. These compounds or HNO-derived from these compounds react with thiols, including glutathione, thiol-containing enzymes and heme-containing proteins in a similar fashion to other acyloxy nitroso compounds. HNO released from these acyloxy nitroso compounds inhibits activated platelet aggregation. These acyloxy nitroso compounds augment the range of release for this group of HNO donors and should be valuable tools in the further study of HNO biology.

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“…The unique biological effects of nitroxyl (HNO) and its potential to be a cell-signaling molecule distinct from nitric oxide (NO) are receiving increasing attention [1–6]. For example, HNO has documented efficacy for the treatment of heart failure [7–11] and alcoholism [12].…”

Section: Introductionmentioning

confidence: 99%

Nitroxyl (HNO) acutely activates the glucose uptake activity of GLUT1

et al. 2012

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Nitroxyl (HNO) is a molecule of significant interest due to its unique pharmacological properties, particularly within the cardiovascular system. A large portion of HNO biological effects can be attributed to its reactivity with protein thiols, where it can generate disulfide bonds. Evidence from studies in erythrocytes suggests that the activity of GLUT1 is enhanced by the formation of an internal disulfide bond. However, there are no reports that document the effects of HNO on glucose uptake. Therefore, we examined the acute effects of Angeli’s salt (AS), a HNO donor, on glucose uptake activity of GLUT1 in L929 fibroblast cells. We report that AS stimulates glucose uptake with a maximum effective concentration of 5.0 mM. An initial 7.2-fold increase occurs within 2 min, which decreases and plateaus to a 4.0-fold activation after 10 min. About 60% of the 4.0-fold activation recovers within 10 min, and 40% remains after an hour. The activation is blocked by the pretreatment of cells with thiol-reactive compounds, iodoacetamide (0.75 mM), cinnamaldehyde (2.0 mM), and phenylarsine oxide (10 μM). The effects of AS are not additive to the stimulatory effects of other acute activators of glucose uptake in L929 cells, such as azide (5 mM), berberine (50 μM), or glucose deprivation. These data suggest that GLUT1 is acutely activated in L929 cells by the formation of a disulfide bond, likely within GLUT1 itself.

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Nitroxyl (HNO) signaling

Cited by 49 publications

References 72 publications

The nitroxyl donor, Angeli’s salt, reduces chronic constriction injury-induced neuropathic pain

The nitroxyl donor, Angeli’s salt, reduces chronic constriction injury-induced neuropathic pain

New acyloxy nitroso compounds with improved water solubility and nitroxyl (HNO) release kinetics and inhibitors of platelet aggregation

Nitroxyl (HNO) acutely activates the glucose uptake activity of GLUT1

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