The emergence of nitroxyl (HNO) as a pharmacological agent

Christopher H. Switzer, Wilmarie Flores-Santana, Daniele Mancardi, Sonia Donzelli, Debashree Basudhar, Lisa A. Ridnour, Katrina M. Miranda, Jon M. Fukuto, Nazareno Paolocci, David A. Wink

Research output: Contribution to journalArticle

Abstract

Once a virtually unknown nitrogen oxide, nitroxyl (HNO) has emerged as a potential pharmacological agent. Recent advances in the understanding of the chemistry of HNO has led to the an understanding of HNO biochemistry which is vastly different from the known chemistry and biochemistry of nitric oxide (NO), the one-electron oxidation product of HNO. The cardiovascular roles of NO have been extensively studied, as NO is a key modulator of vascular tone and is involved in a number of vascular related pathologies. HNO displays unique cardiovascular properties and has been shown to have positive lusitropic and ionotropic effects in failing hearts without a chronotropic effect. Additionally, HNO causes a release of CGRP and modulates calcium channels such as ryanodine receptors. HNO has shown beneficial effects in ischemia reperfusion injury, as HNO treatment before ischemia-reperfusion reduces infarct size. In addition to the cardiovascular effects observed, HNO has shown initial promise in the realm of cancer therapy. HNO has been demonstrated to inhibit GAPDH, a key glycolytic enzyme. Due to the Warburg effect, inhibiting glycolysis is an attractive target for inhibiting tumor proliferation. Indeed, HNO has recently been shown to inhibit tumor proliferation in mouse xenografts. Additionally, HNO inhibits tumor angiogenesis and induces cancer cell apoptosis. The effects seen with HNO donors are quite different from NO donors and in some cases are opposite. The chemical nature of HNO explains how HNO and NO, although closely chemically related, act so differently in biochemical systems. This also gives insight into the potential molecular motifs that may be reactive towards HNO and opens up a novel field of pharmacological development.

Original languageEnglish (US)
Pages (from-to)835-840
Number of pages6
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1787
Issue number7
DOIs
StatePublished - Jul 2009

Fingerprint

Nitric Oxide
Pharmacology
Tumors
Biochemistry
Neoplasms
Blood Vessels
Ryanodine Receptor Calcium Release Channel
Nitric Oxide Donors
Pathology
Glycolysis
Calcium Channels
Reperfusion Injury
Heterografts
Modulators
Reperfusion
Ischemia
Cells
nitroxyl
Electrons
Apoptosis

Keywords

  • Heart failure
  • Ischemia reperfusion injury
  • Nitric oxide
  • Nitroxyl

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Switzer, C. H., Flores-Santana, W., Mancardi, D., Donzelli, S., Basudhar, D., Ridnour, L. A., ... Wink, D. A. (2009). The emergence of nitroxyl (HNO) as a pharmacological agent. Biochimica et Biophysica Acta - Bioenergetics, 1787(7), 835-840. https://doi.org/10.1016/j.bbabio.2009.04.015

The emergence of nitroxyl (HNO) as a pharmacological agent. / Switzer, Christopher H.; Flores-Santana, Wilmarie; Mancardi, Daniele; Donzelli, Sonia; Basudhar, Debashree; Ridnour, Lisa A.; Miranda, Katrina M.; Fukuto, Jon M.; Paolocci, Nazareno; Wink, David A.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1787, No. 7, 07.2009, p. 835-840.

Research output: Contribution to journalArticle

Switzer, CH, Flores-Santana, W, Mancardi, D, Donzelli, S, Basudhar, D, Ridnour, LA, Miranda, KM, Fukuto, JM, Paolocci, N & Wink, DA 2009, 'The emergence of nitroxyl (HNO) as a pharmacological agent', Biochimica et Biophysica Acta - Bioenergetics, vol. 1787, no. 7, pp. 835-840. https://doi.org/10.1016/j.bbabio.2009.04.015
Switzer CH, Flores-Santana W, Mancardi D, Donzelli S, Basudhar D, Ridnour LA et al. The emergence of nitroxyl (HNO) as a pharmacological agent. Biochimica et Biophysica Acta - Bioenergetics. 2009 Jul;1787(7):835-840. https://doi.org/10.1016/j.bbabio.2009.04.015
Switzer, Christopher H. ; Flores-Santana, Wilmarie ; Mancardi, Daniele ; Donzelli, Sonia ; Basudhar, Debashree ; Ridnour, Lisa A. ; Miranda, Katrina M. ; Fukuto, Jon M. ; Paolocci, Nazareno ; Wink, David A. / The emergence of nitroxyl (HNO) as a pharmacological agent. In: Biochimica et Biophysica Acta - Bioenergetics. 2009 ; Vol. 1787, No. 7. pp. 835-840.
@article{875f086eb90d4037926eced76abe8f17,
title = "The emergence of nitroxyl (HNO) as a pharmacological agent",
abstract = "Once a virtually unknown nitrogen oxide, nitroxyl (HNO) has emerged as a potential pharmacological agent. Recent advances in the understanding of the chemistry of HNO has led to the an understanding of HNO biochemistry which is vastly different from the known chemistry and biochemistry of nitric oxide (NO), the one-electron oxidation product of HNO. The cardiovascular roles of NO have been extensively studied, as NO is a key modulator of vascular tone and is involved in a number of vascular related pathologies. HNO displays unique cardiovascular properties and has been shown to have positive lusitropic and ionotropic effects in failing hearts without a chronotropic effect. Additionally, HNO causes a release of CGRP and modulates calcium channels such as ryanodine receptors. HNO has shown beneficial effects in ischemia reperfusion injury, as HNO treatment before ischemia-reperfusion reduces infarct size. In addition to the cardiovascular effects observed, HNO has shown initial promise in the realm of cancer therapy. HNO has been demonstrated to inhibit GAPDH, a key glycolytic enzyme. Due to the Warburg effect, inhibiting glycolysis is an attractive target for inhibiting tumor proliferation. Indeed, HNO has recently been shown to inhibit tumor proliferation in mouse xenografts. Additionally, HNO inhibits tumor angiogenesis and induces cancer cell apoptosis. The effects seen with HNO donors are quite different from NO donors and in some cases are opposite. The chemical nature of HNO explains how HNO and NO, although closely chemically related, act so differently in biochemical systems. This also gives insight into the potential molecular motifs that may be reactive towards HNO and opens up a novel field of pharmacological development.",
keywords = "Heart failure, Ischemia reperfusion injury, Nitric oxide, Nitroxyl",
author = "Switzer, {Christopher H.} and Wilmarie Flores-Santana and Daniele Mancardi and Sonia Donzelli and Debashree Basudhar and Ridnour, {Lisa A.} and Miranda, {Katrina M.} and Fukuto, {Jon M.} and Nazareno Paolocci and Wink, {David A.}",
year = "2009",
month = "7",
doi = "10.1016/j.bbabio.2009.04.015",
language = "English (US)",
volume = "1787",
pages = "835--840",
journal = "Biochimica et Biophysica Acta - Bioenergetics",
issn = "0005-2728",
publisher = "Elsevier",
number = "7",

}

TY - JOUR

T1 - The emergence of nitroxyl (HNO) as a pharmacological agent

AU - Switzer, Christopher H.

AU - Flores-Santana, Wilmarie

AU - Mancardi, Daniele

AU - Donzelli, Sonia

AU - Basudhar, Debashree

AU - Ridnour, Lisa A.

AU - Miranda, Katrina M.

AU - Fukuto, Jon M.

AU - Paolocci, Nazareno

AU - Wink, David A.

PY - 2009/7

Y1 - 2009/7

N2 - Once a virtually unknown nitrogen oxide, nitroxyl (HNO) has emerged as a potential pharmacological agent. Recent advances in the understanding of the chemistry of HNO has led to the an understanding of HNO biochemistry which is vastly different from the known chemistry and biochemistry of nitric oxide (NO), the one-electron oxidation product of HNO. The cardiovascular roles of NO have been extensively studied, as NO is a key modulator of vascular tone and is involved in a number of vascular related pathologies. HNO displays unique cardiovascular properties and has been shown to have positive lusitropic and ionotropic effects in failing hearts without a chronotropic effect. Additionally, HNO causes a release of CGRP and modulates calcium channels such as ryanodine receptors. HNO has shown beneficial effects in ischemia reperfusion injury, as HNO treatment before ischemia-reperfusion reduces infarct size. In addition to the cardiovascular effects observed, HNO has shown initial promise in the realm of cancer therapy. HNO has been demonstrated to inhibit GAPDH, a key glycolytic enzyme. Due to the Warburg effect, inhibiting glycolysis is an attractive target for inhibiting tumor proliferation. Indeed, HNO has recently been shown to inhibit tumor proliferation in mouse xenografts. Additionally, HNO inhibits tumor angiogenesis and induces cancer cell apoptosis. The effects seen with HNO donors are quite different from NO donors and in some cases are opposite. The chemical nature of HNO explains how HNO and NO, although closely chemically related, act so differently in biochemical systems. This also gives insight into the potential molecular motifs that may be reactive towards HNO and opens up a novel field of pharmacological development.

AB - Once a virtually unknown nitrogen oxide, nitroxyl (HNO) has emerged as a potential pharmacological agent. Recent advances in the understanding of the chemistry of HNO has led to the an understanding of HNO biochemistry which is vastly different from the known chemistry and biochemistry of nitric oxide (NO), the one-electron oxidation product of HNO. The cardiovascular roles of NO have been extensively studied, as NO is a key modulator of vascular tone and is involved in a number of vascular related pathologies. HNO displays unique cardiovascular properties and has been shown to have positive lusitropic and ionotropic effects in failing hearts without a chronotropic effect. Additionally, HNO causes a release of CGRP and modulates calcium channels such as ryanodine receptors. HNO has shown beneficial effects in ischemia reperfusion injury, as HNO treatment before ischemia-reperfusion reduces infarct size. In addition to the cardiovascular effects observed, HNO has shown initial promise in the realm of cancer therapy. HNO has been demonstrated to inhibit GAPDH, a key glycolytic enzyme. Due to the Warburg effect, inhibiting glycolysis is an attractive target for inhibiting tumor proliferation. Indeed, HNO has recently been shown to inhibit tumor proliferation in mouse xenografts. Additionally, HNO inhibits tumor angiogenesis and induces cancer cell apoptosis. The effects seen with HNO donors are quite different from NO donors and in some cases are opposite. The chemical nature of HNO explains how HNO and NO, although closely chemically related, act so differently in biochemical systems. This also gives insight into the potential molecular motifs that may be reactive towards HNO and opens up a novel field of pharmacological development.

KW - Heart failure

KW - Ischemia reperfusion injury

KW - Nitric oxide

KW - Nitroxyl

UR - http://www.scopus.com/inward/record.url?scp=67649297949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649297949&partnerID=8YFLogxK

U2 - 10.1016/j.bbabio.2009.04.015

DO - 10.1016/j.bbabio.2009.04.015

M3 - Article

C2 - 19426703

AN - SCOPUS:67649297949

VL - 1787

SP - 835

EP - 840

JO - Biochimica et Biophysica Acta - Bioenergetics

JF - Biochimica et Biophysica Acta - Bioenergetics

SN - 0005-2728

IS - 7

ER -