The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction

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The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction. / Talib, Jihan; Kwan, Jair; Suryo Rahmanto, Aldwin; Witting, Paul K; Davies, Michael Jonathan.

In: Biochemical Journal, Vol. 457, No. 1, 01.01.2014, p. 89-97.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Talib, J, Kwan, J, Suryo Rahmanto, A, Witting, PK & Davies, MJ 2014, 'The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction', Biochemical Journal, vol. 457, no. 1, pp. 89-97. https://doi.org/10.1042/BJ20131135

APA

Talib, J., Kwan, J., Suryo Rahmanto, A., Witting, P. K., & Davies, M. J. (2014). The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction. Biochemical Journal, 457(1), 89-97. https://doi.org/10.1042/BJ20131135

Vancouver

Talib J, Kwan J, Suryo Rahmanto A, Witting PK, Davies MJ. The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction. Biochemical Journal. 2014 Jan 1;457(1):89-97. https://doi.org/10.1042/BJ20131135

Author

Talib, Jihan ; Kwan, Jair ; Suryo Rahmanto, Aldwin ; Witting, Paul K ; Davies, Michael Jonathan. / The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction. In: Biochemical Journal. 2014 ; Vol. 457, No. 1. pp. 89-97.

Bibtex

@article{53ad9548c0324e5d8f93cfcd009e5200,
title = "The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction",
abstract = "Smokers have an elevated risk of cardiovascular disease but the origin(s) of this increased risk are incompletely defined. Considerable evidence supports an accumulation of the oxidant-generating enzyme MPO (myeloperoxidase) in the inflamed artery wall, and smokers have high levels of SCN(-), a preferred MPO substrate, with this resulting in HOSCN (hypothiocyanous acid) formation. We hypothesized that this thiol-specific oxidant may target the Zn(2+)-thiol cluster of eNOS (endothelial nitric oxide synthase), resulting in enzyme dysfunction and reduced formation of the critical signalling molecule NO•. Decreased NO• bioavailability is an early and critical event in atherogenesis, and HOSCN-mediated damage to eNOS may contribute to smoking-associated disease. In the present study it is shown that exposure of isolated eNOS to HOSCN or MPO/H2O2/SCN(-) decreased active dimeric eNOS levels, and increased inactive monomer and Zn(2+) release, compared with controls, HOCl (hypochlorous acid)- or MPO/H2O2/Cl(-)-treated samples. eNOS activity was increasingly compromised by MPO/H2O2/Cl(-) with increasing SCN(-) concentrations. Exposure of HCAEC (human coronary artery endothelial cell) lysates to pre-formed HOSCN, or MPO/H2O2/Cl(-) with increasing SCN(-), increased eNOS monomerization and Zn(2+) release, and decreased activity. Intact HCAECs exposed to HOCl and HOSCN had decreased eNOS activity and NO2(-)/NO3(-) formation (products of NO• decomposition), and increased free Zn(2+). Exposure of isolated rat aortic rings to HOSCN resulted in thiol loss, and decreased eNOS activity and cGMP levels. Overall these data indicate that high SCN(-) levels, as seen in smokers, can increase HOSCN formation and enhance eNOS dysfunction in human endothelial cells, with this potentially contributing to increased atherogenesis in smokers.",
keywords = "Animals, Cells, Cultured, Enzyme Activation, Humans, Hypochlorous Acid, Male, Nitric Oxide Synthase Type III, Oxidants, Peroxidase, Protein Multimerization, Rats, Rats, Wistar, Smoking, Thiocyanates",
author = "Jihan Talib and Jair Kwan and {Suryo Rahmanto}, Aldwin and Witting, {Paul K} and Davies, {Michael Jonathan}",
year = "2014",
month = "1",
day = "1",
doi = "10.1042/BJ20131135",
language = "English",
volume = "457",
pages = "89--97",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction

AU - Talib, Jihan

AU - Kwan, Jair

AU - Suryo Rahmanto, Aldwin

AU - Witting, Paul K

AU - Davies, Michael Jonathan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Smokers have an elevated risk of cardiovascular disease but the origin(s) of this increased risk are incompletely defined. Considerable evidence supports an accumulation of the oxidant-generating enzyme MPO (myeloperoxidase) in the inflamed artery wall, and smokers have high levels of SCN(-), a preferred MPO substrate, with this resulting in HOSCN (hypothiocyanous acid) formation. We hypothesized that this thiol-specific oxidant may target the Zn(2+)-thiol cluster of eNOS (endothelial nitric oxide synthase), resulting in enzyme dysfunction and reduced formation of the critical signalling molecule NO•. Decreased NO• bioavailability is an early and critical event in atherogenesis, and HOSCN-mediated damage to eNOS may contribute to smoking-associated disease. In the present study it is shown that exposure of isolated eNOS to HOSCN or MPO/H2O2/SCN(-) decreased active dimeric eNOS levels, and increased inactive monomer and Zn(2+) release, compared with controls, HOCl (hypochlorous acid)- or MPO/H2O2/Cl(-)-treated samples. eNOS activity was increasingly compromised by MPO/H2O2/Cl(-) with increasing SCN(-) concentrations. Exposure of HCAEC (human coronary artery endothelial cell) lysates to pre-formed HOSCN, or MPO/H2O2/Cl(-) with increasing SCN(-), increased eNOS monomerization and Zn(2+) release, and decreased activity. Intact HCAECs exposed to HOCl and HOSCN had decreased eNOS activity and NO2(-)/NO3(-) formation (products of NO• decomposition), and increased free Zn(2+). Exposure of isolated rat aortic rings to HOSCN resulted in thiol loss, and decreased eNOS activity and cGMP levels. Overall these data indicate that high SCN(-) levels, as seen in smokers, can increase HOSCN formation and enhance eNOS dysfunction in human endothelial cells, with this potentially contributing to increased atherogenesis in smokers.

AB - Smokers have an elevated risk of cardiovascular disease but the origin(s) of this increased risk are incompletely defined. Considerable evidence supports an accumulation of the oxidant-generating enzyme MPO (myeloperoxidase) in the inflamed artery wall, and smokers have high levels of SCN(-), a preferred MPO substrate, with this resulting in HOSCN (hypothiocyanous acid) formation. We hypothesized that this thiol-specific oxidant may target the Zn(2+)-thiol cluster of eNOS (endothelial nitric oxide synthase), resulting in enzyme dysfunction and reduced formation of the critical signalling molecule NO•. Decreased NO• bioavailability is an early and critical event in atherogenesis, and HOSCN-mediated damage to eNOS may contribute to smoking-associated disease. In the present study it is shown that exposure of isolated eNOS to HOSCN or MPO/H2O2/SCN(-) decreased active dimeric eNOS levels, and increased inactive monomer and Zn(2+) release, compared with controls, HOCl (hypochlorous acid)- or MPO/H2O2/Cl(-)-treated samples. eNOS activity was increasingly compromised by MPO/H2O2/Cl(-) with increasing SCN(-) concentrations. Exposure of HCAEC (human coronary artery endothelial cell) lysates to pre-formed HOSCN, or MPO/H2O2/Cl(-) with increasing SCN(-), increased eNOS monomerization and Zn(2+) release, and decreased activity. Intact HCAECs exposed to HOCl and HOSCN had decreased eNOS activity and NO2(-)/NO3(-) formation (products of NO• decomposition), and increased free Zn(2+). Exposure of isolated rat aortic rings to HOSCN resulted in thiol loss, and decreased eNOS activity and cGMP levels. Overall these data indicate that high SCN(-) levels, as seen in smokers, can increase HOSCN formation and enhance eNOS dysfunction in human endothelial cells, with this potentially contributing to increased atherogenesis in smokers.

KW - Animals

KW - Cells, Cultured

KW - Enzyme Activation

KW - Humans

KW - Hypochlorous Acid

KW - Male

KW - Nitric Oxide Synthase Type III

KW - Oxidants

KW - Peroxidase

KW - Protein Multimerization

KW - Rats

KW - Rats, Wistar

KW - Smoking

KW - Thiocyanates

U2 - 10.1042/BJ20131135

DO - 10.1042/BJ20131135

M3 - Journal article

VL - 457

SP - 89

EP - 97

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -

ID: 128974154