Myeloperoxidase-derived damage to human plasma fibronectin: Modulation by protein binding and thiocyanate ions (SCN)

Research output: Contribution to journalJournal articlepeer-review

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Myeloperoxidase-derived damage to human plasma fibronectin : Modulation by protein binding and thiocyanate ions (SCN). / Vanichkitrungruang, Siriluck; Chuang, Christine Y.; Hawkins, Clare L.; Davies, Michael J.

In: Redox Biology, Vol. 36, 101641, 2020.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Vanichkitrungruang, S, Chuang, CY, Hawkins, CL & Davies, MJ 2020, 'Myeloperoxidase-derived damage to human plasma fibronectin: Modulation by protein binding and thiocyanate ions (SCN)', Redox Biology, vol. 36, 101641. https://doi.org/10.1016/j.redox.2020.101641

APA

Vanichkitrungruang, S., Chuang, C. Y., Hawkins, C. L., & Davies, M. J. (2020). Myeloperoxidase-derived damage to human plasma fibronectin: Modulation by protein binding and thiocyanate ions (SCN). Redox Biology, 36, [101641]. https://doi.org/10.1016/j.redox.2020.101641

Vancouver

Vanichkitrungruang S, Chuang CY, Hawkins CL, Davies MJ. Myeloperoxidase-derived damage to human plasma fibronectin: Modulation by protein binding and thiocyanate ions (SCN). Redox Biology. 2020;36. 101641. https://doi.org/10.1016/j.redox.2020.101641

Author

Vanichkitrungruang, Siriluck ; Chuang, Christine Y. ; Hawkins, Clare L. ; Davies, Michael J. / Myeloperoxidase-derived damage to human plasma fibronectin : Modulation by protein binding and thiocyanate ions (SCN). In: Redox Biology. 2020 ; Vol. 36.

Bibtex

@article{d0e5f7dba6df40209696524824851437,
title = "Myeloperoxidase-derived damage to human plasma fibronectin: Modulation by protein binding and thiocyanate ions (SCN−)",
abstract = "Endothelial cell dysfunction is an early event in cardiovascular disease and atherosclerosis. The origin of this dysfunction is unresolved, but accumulating evidence implicates damaging oxidants, including hypochlorous acid (HOCl), a major oxidant produced by myeloperoxidase (MPO), during chronic inflammation. MPO is released extracellularly by activated leukocytes and binds to extracellular molecules including fibronectin, a major matrix glycoprotein involved in endothelial cell binding. We hypothesized that MPO binding might influence the modifications induced on fibronectin, when compared to reagent HOCl, with this including alterations to the extent of damage to protein side-chains, modified structural integrity, changes to functional domains, and impact on na{\"i}ve human coronary artery endothelial cell (HCAEC) adhesion and metabolic activity. The effect of increasing concentrations of the alternative MPO substrate thiocyanate (SCN−), which might decrease HOCl formation were also examined. Exposure of fibronectin to MPO/H2O2/Cl− is shown to result in damage to the functionally important cell-binding and heparin-binding fragments, gross structural changes to the protein, and altered HCAEC adhesion and activity. Differences were observed between stoichiometric, and above-stoichiometric MPO concentrations consistent with an effect of MPO binding to fibronectin. In contrast, MPO/H2O2/SCN− induced much less marked changes and limited protein damage. Addition of increasing SCN− concentrations to the MPO/H2O2/Cl− system provided protection, with 20 μM of this anion rescuing damage to functionally-important domains, decreasing chemical modification, and maintaining normal HCAEC behavior. Modulating MPO binding to fibronectin, or enhancing SCN− levels at sites of inflammation may therefore limit MPO-mediated damage, and be of therapeutic value.",
keywords = "Endothelial cell, Extracellular matrix, Fibronectin, Hypochlorous acid, Hypothiocyanous acid, Myeloperoxidase, Protein oxidation",
author = "Siriluck Vanichkitrungruang and Chuang, {Christine Y.} and Hawkins, {Clare L.} and Davies, {Michael J.}",
year = "2020",
doi = "10.1016/j.redox.2020.101641",
language = "English",
volume = "36",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Myeloperoxidase-derived damage to human plasma fibronectin

T2 - Modulation by protein binding and thiocyanate ions (SCN−)

AU - Vanichkitrungruang, Siriluck

AU - Chuang, Christine Y.

AU - Hawkins, Clare L.

AU - Davies, Michael J.

PY - 2020

Y1 - 2020

N2 - Endothelial cell dysfunction is an early event in cardiovascular disease and atherosclerosis. The origin of this dysfunction is unresolved, but accumulating evidence implicates damaging oxidants, including hypochlorous acid (HOCl), a major oxidant produced by myeloperoxidase (MPO), during chronic inflammation. MPO is released extracellularly by activated leukocytes and binds to extracellular molecules including fibronectin, a major matrix glycoprotein involved in endothelial cell binding. We hypothesized that MPO binding might influence the modifications induced on fibronectin, when compared to reagent HOCl, with this including alterations to the extent of damage to protein side-chains, modified structural integrity, changes to functional domains, and impact on naïve human coronary artery endothelial cell (HCAEC) adhesion and metabolic activity. The effect of increasing concentrations of the alternative MPO substrate thiocyanate (SCN−), which might decrease HOCl formation were also examined. Exposure of fibronectin to MPO/H2O2/Cl− is shown to result in damage to the functionally important cell-binding and heparin-binding fragments, gross structural changes to the protein, and altered HCAEC adhesion and activity. Differences were observed between stoichiometric, and above-stoichiometric MPO concentrations consistent with an effect of MPO binding to fibronectin. In contrast, MPO/H2O2/SCN− induced much less marked changes and limited protein damage. Addition of increasing SCN− concentrations to the MPO/H2O2/Cl− system provided protection, with 20 μM of this anion rescuing damage to functionally-important domains, decreasing chemical modification, and maintaining normal HCAEC behavior. Modulating MPO binding to fibronectin, or enhancing SCN− levels at sites of inflammation may therefore limit MPO-mediated damage, and be of therapeutic value.

AB - Endothelial cell dysfunction is an early event in cardiovascular disease and atherosclerosis. The origin of this dysfunction is unresolved, but accumulating evidence implicates damaging oxidants, including hypochlorous acid (HOCl), a major oxidant produced by myeloperoxidase (MPO), during chronic inflammation. MPO is released extracellularly by activated leukocytes and binds to extracellular molecules including fibronectin, a major matrix glycoprotein involved in endothelial cell binding. We hypothesized that MPO binding might influence the modifications induced on fibronectin, when compared to reagent HOCl, with this including alterations to the extent of damage to protein side-chains, modified structural integrity, changes to functional domains, and impact on naïve human coronary artery endothelial cell (HCAEC) adhesion and metabolic activity. The effect of increasing concentrations of the alternative MPO substrate thiocyanate (SCN−), which might decrease HOCl formation were also examined. Exposure of fibronectin to MPO/H2O2/Cl− is shown to result in damage to the functionally important cell-binding and heparin-binding fragments, gross structural changes to the protein, and altered HCAEC adhesion and activity. Differences were observed between stoichiometric, and above-stoichiometric MPO concentrations consistent with an effect of MPO binding to fibronectin. In contrast, MPO/H2O2/SCN− induced much less marked changes and limited protein damage. Addition of increasing SCN− concentrations to the MPO/H2O2/Cl− system provided protection, with 20 μM of this anion rescuing damage to functionally-important domains, decreasing chemical modification, and maintaining normal HCAEC behavior. Modulating MPO binding to fibronectin, or enhancing SCN− levels at sites of inflammation may therefore limit MPO-mediated damage, and be of therapeutic value.

KW - Endothelial cell

KW - Extracellular matrix

KW - Fibronectin

KW - Hypochlorous acid

KW - Hypothiocyanous acid

KW - Myeloperoxidase

KW - Protein oxidation

UR - http://www.scopus.com/inward/record.url?scp=85088270656&partnerID=8YFLogxK

U2 - 10.1016/j.redox.2020.101641

DO - 10.1016/j.redox.2020.101641

M3 - Journal article

C2 - 32863239

AN - SCOPUS:85088270656

VL - 36

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

M1 - 101641

ER -

ID: 251307892