Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase

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Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase. / Nybo, Tina; Dieterich, Simon; Gamon, Luke F.; Chuang, Christine Y.; Hammer, Astrid; Hoefler, Gerald; Malle, Ernst; Rogowska-Wrzesinska, Adelina; Davies, Michael J.

In: Redox Biology, Vol. 20, 2019, p. 496-513.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nybo, T, Dieterich, S, Gamon, LF, Chuang, CY, Hammer, A, Hoefler, G, Malle, E, Rogowska-Wrzesinska, A & Davies, MJ 2019, 'Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase', Redox Biology, vol. 20, pp. 496-513. https://doi.org/10.1016/j.redox.2018.10.022

APA

Nybo, T., Dieterich, S., Gamon, L. F., Chuang, C. Y., Hammer, A., Hoefler, G., Malle, E., Rogowska-Wrzesinska, A., & Davies, M. J. (2019). Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase. Redox Biology, 20, 496-513. https://doi.org/10.1016/j.redox.2018.10.022

Vancouver

Nybo T, Dieterich S, Gamon LF, Chuang CY, Hammer A, Hoefler G et al. Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase. Redox Biology. 2019;20:496-513. https://doi.org/10.1016/j.redox.2018.10.022

Author

Nybo, Tina ; Dieterich, Simon ; Gamon, Luke F. ; Chuang, Christine Y. ; Hammer, Astrid ; Hoefler, Gerald ; Malle, Ernst ; Rogowska-Wrzesinska, Adelina ; Davies, Michael J. / Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase. In: Redox Biology. 2019 ; Vol. 20. pp. 496-513.

Bibtex

@article{ffb7ad5d092948ecb3bfa5dabc55763b,
title = "Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase",
abstract = "Basement membranes are specialized extracellular matrices that underlie arterial wall endothelial cells, with laminin being a key structural and biologically-active component. Hypochlorous acid (HOCl), a potent oxidizing and chlorinating agent, is formed in vivo at sites of inflammation via the enzymatic action of myeloperoxidase (MPO), released by activated leukocytes. Considerable data supports a role for MPO-derived oxidants in cardiovascular disease and particularly atherosclerosis. These effects may be mediated via extracellular matrix damage to which MPO binds. Herein we detect and quantify sites of oxidation and chlorination on isolated laminin-111, and laminin in basement membrane extracts (BME), by use of mass spectrometry. Increased modification was detected with increasing oxidant exposure. Mass mapping indicated selectivity in the sites and extent of damage; Met residues were most heavily modified. Fewer modifications were detected with BME, possibly due to the shielding effects. HOCl oxidised 30 (of 56 total) Met and 7 (of 24) Trp residues, and chlorinated 33 (of 99) Tyr residues; 3 Tyr were dichlorinated. An additional 8 Met and 10 Trp oxidations, 14 chlorinations, and 18 dichlorinations were detected with the MPO/H2O2/Cl- system when compared to reagent HOCl. Interestingly, chlorination was detected at Tyr(2415) in the integrin-binding region; this may decrease cellular adhesion. Co-localization of MPO-damaged epitopes and laminin was detected in human atherosclerotic lesions. These data indicate that laminin is extensively modified by MPO-derived oxidants, with structural and Junctional changes. These modifications, and compromised cell-matrix interactions, may promote endothelial cell dysfunction, weaken the structure of atherosclerotic lesions, and enhance lesion rupture.",
keywords = "Extracellular matrix, Hypochlorous acid, Laminin, Protein oxidation, 3-chlorotyrosine, Myeloperoxidase",
author = "Tina Nybo and Simon Dieterich and Gamon, {Luke F.} and Chuang, {Christine Y.} and Astrid Hammer and Gerald Hoefler and Ernst Malle and Adelina Rogowska-Wrzesinska and Davies, {Michael J.}",
year = "2019",
doi = "10.1016/j.redox.2018.10.022",
language = "English",
volume = "20",
pages = "496--513",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase

AU - Nybo, Tina

AU - Dieterich, Simon

AU - Gamon, Luke F.

AU - Chuang, Christine Y.

AU - Hammer, Astrid

AU - Hoefler, Gerald

AU - Malle, Ernst

AU - Rogowska-Wrzesinska, Adelina

AU - Davies, Michael J.

PY - 2019

Y1 - 2019

N2 - Basement membranes are specialized extracellular matrices that underlie arterial wall endothelial cells, with laminin being a key structural and biologically-active component. Hypochlorous acid (HOCl), a potent oxidizing and chlorinating agent, is formed in vivo at sites of inflammation via the enzymatic action of myeloperoxidase (MPO), released by activated leukocytes. Considerable data supports a role for MPO-derived oxidants in cardiovascular disease and particularly atherosclerosis. These effects may be mediated via extracellular matrix damage to which MPO binds. Herein we detect and quantify sites of oxidation and chlorination on isolated laminin-111, and laminin in basement membrane extracts (BME), by use of mass spectrometry. Increased modification was detected with increasing oxidant exposure. Mass mapping indicated selectivity in the sites and extent of damage; Met residues were most heavily modified. Fewer modifications were detected with BME, possibly due to the shielding effects. HOCl oxidised 30 (of 56 total) Met and 7 (of 24) Trp residues, and chlorinated 33 (of 99) Tyr residues; 3 Tyr were dichlorinated. An additional 8 Met and 10 Trp oxidations, 14 chlorinations, and 18 dichlorinations were detected with the MPO/H2O2/Cl- system when compared to reagent HOCl. Interestingly, chlorination was detected at Tyr(2415) in the integrin-binding region; this may decrease cellular adhesion. Co-localization of MPO-damaged epitopes and laminin was detected in human atherosclerotic lesions. These data indicate that laminin is extensively modified by MPO-derived oxidants, with structural and Junctional changes. These modifications, and compromised cell-matrix interactions, may promote endothelial cell dysfunction, weaken the structure of atherosclerotic lesions, and enhance lesion rupture.

AB - Basement membranes are specialized extracellular matrices that underlie arterial wall endothelial cells, with laminin being a key structural and biologically-active component. Hypochlorous acid (HOCl), a potent oxidizing and chlorinating agent, is formed in vivo at sites of inflammation via the enzymatic action of myeloperoxidase (MPO), released by activated leukocytes. Considerable data supports a role for MPO-derived oxidants in cardiovascular disease and particularly atherosclerosis. These effects may be mediated via extracellular matrix damage to which MPO binds. Herein we detect and quantify sites of oxidation and chlorination on isolated laminin-111, and laminin in basement membrane extracts (BME), by use of mass spectrometry. Increased modification was detected with increasing oxidant exposure. Mass mapping indicated selectivity in the sites and extent of damage; Met residues were most heavily modified. Fewer modifications were detected with BME, possibly due to the shielding effects. HOCl oxidised 30 (of 56 total) Met and 7 (of 24) Trp residues, and chlorinated 33 (of 99) Tyr residues; 3 Tyr were dichlorinated. An additional 8 Met and 10 Trp oxidations, 14 chlorinations, and 18 dichlorinations were detected with the MPO/H2O2/Cl- system when compared to reagent HOCl. Interestingly, chlorination was detected at Tyr(2415) in the integrin-binding region; this may decrease cellular adhesion. Co-localization of MPO-damaged epitopes and laminin was detected in human atherosclerotic lesions. These data indicate that laminin is extensively modified by MPO-derived oxidants, with structural and Junctional changes. These modifications, and compromised cell-matrix interactions, may promote endothelial cell dysfunction, weaken the structure of atherosclerotic lesions, and enhance lesion rupture.

KW - Extracellular matrix

KW - Hypochlorous acid

KW - Laminin

KW - Protein oxidation

KW - 3-chlorotyrosine

KW - Myeloperoxidase

U2 - 10.1016/j.redox.2018.10.022

DO - 10.1016/j.redox.2018.10.022

M3 - Journal article

C2 - 30476874

VL - 20

SP - 496

EP - 513

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

ER -

ID: 229271383