Peroxynitrous acid (ONOOH) modifies the structure of anastellin and influences its capacity to polymerize fibronectin

Jianfei He; Eva Ramos Becares; Peter Waaben Thulstrup; Luke F. Gamon; Jannik Nedergaard Pedersen; Daniel Otzen; Pontus Gourdon; Michael J. Davies; Per Hägglund

doi:10.1016/j.redox.2020.101631

Peroxynitrous acid (ONOOH) modifies the structure of anastellin and influences its capacity to polymerize fibronectin

Jianfei He, Eva Ramos Becares, Peter Waaben Thulstrup, Luke F. Gamon, Jannik Nedergaard Pedersen, Daniel Otzen, Pontus Gourdon, Michael J. Davies^*, Per Hägglund^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

8 Citationer (Scopus)

Abstract

Anastellin (AN), a fragment of the first type III module in fibronectin (FN), initiates formation of superfibronectin, a polymer which resembles the native cell-derived fibrillar FN found in the extracellular matrix of many tissues, but which displays remarkably different functional properties. Here we demonstrate that exposure of AN to the biologically-important inflammatory oxidant, peroxynitrous acid (ONOOH), either as a bolus or formed at low levels in a time-dependent manner from SIN-1, impairs the capability of AN to polymerize FN. In contrast, exposure of FN to ONOOH does not seem to affect superfibronectin formation to the same extent. This oxidant-induced loss-of-function in AN occurs in a dose-dependent manner, and correlates with structural perturbations, loss of the amino acid tyrosine and tryptophan, and dose-dependent formation of modified amino acid side-chains (3-nitrotyrosine, di-tyrosine and 6-nitrotryptophan). Reagent ONOOH also induces formation of oligomeric species which decrease in the presence of bicarbonate, whereas SIN-1 mainly generates dimers. Modifications were detected at sub-stoichiometric (0.1-fold), or greater, molar excesses of oxidant compared to AN. These species have been localized to specific sites by peptide mass mapping. With high levels of oxidant (>100 times molar excess), ONOOH also induces unfolding of the beta-sheet structure of AN, thermal destabilization, and formation of high molecular mass aggregates. These results have important implications for the understanding of FN fibrillogenesis in vivo, and indicates that AN is highly sensitive to pathophysiological levels of oxidants such as ONOOH.

Originalsprog	Engelsk
Artikelnummer	101631
Tidsskrift	Redox Biology
Vol/bind	36
ISSN	2213-2317
DOI	https://doi.org/10.1016/j.redox.2020.101631
Status	Udgivet - sep. 2020

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@article{172564c7946544feaaa33dd96282ac3a,

title = "Peroxynitrous acid (ONOOH) modifies the structure of anastellin and influences its capacity to polymerize fibronectin",

abstract = "Anastellin (AN), a fragment of the first type III module in fibronectin (FN), initiates formation of superfibronectin, a polymer which resembles the native cell-derived fibrillar FN found in the extracellular matrix of many tissues, but which displays remarkably different functional properties. Here we demonstrate that exposure of AN to the biologically-important inflammatory oxidant, peroxynitrous acid (ONOOH), either as a bolus or formed at low levels in a time-dependent manner from SIN-1, impairs the capability of AN to polymerize FN. In contrast, exposure of FN to ONOOH does not seem to affect superfibronectin formation to the same extent. This oxidant-induced loss-of-function in AN occurs in a dose-dependent manner, and correlates with structural perturbations, loss of the amino acid tyrosine and tryptophan, and dose-dependent formation of modified amino acid side-chains (3-nitrotyrosine, di-tyrosine and 6-nitrotryptophan). Reagent ONOOH also induces formation of oligomeric species which decrease in the presence of bicarbonate, whereas SIN-1 mainly generates dimers. Modifications were detected at sub-stoichiometric (0.1-fold), or greater, molar excesses of oxidant compared to AN. These species have been localized to specific sites by peptide mass mapping. With high levels of oxidant (>100 times molar excess), ONOOH also induces unfolding of the beta-sheet structure of AN, thermal destabilization, and formation of high molecular mass aggregates. These results have important implications for the understanding of FN fibrillogenesis in vivo, and indicates that AN is highly sensitive to pathophysiological levels of oxidants such as ONOOH.",

keywords = "Aggregation, Anastellin, Extracellular matrix, Fibronectin, Peroxynitrous acid, Protein oxidation",

author = "Jianfei He and Becares, {Eva Ramos} and Thulstrup, {Peter Waaben} and Gamon, {Luke F.} and Pedersen, {Jannik Nedergaard} and Daniel Otzen and Pontus Gourdon and Davies, {Michael J.} and Per H{\"a}gglund",

year = "2020",

month = sep,

doi = "10.1016/j.redox.2020.101631",

language = "English",

volume = "36",

journal = "Redox Biology",

issn = "2213-2317",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Peroxynitrous acid (ONOOH) modifies the structure of anastellin and influences its capacity to polymerize fibronectin

AU - He, Jianfei

AU - Becares, Eva Ramos

AU - Thulstrup, Peter Waaben

AU - Gamon, Luke F.

AU - Pedersen, Jannik Nedergaard

AU - Otzen, Daniel

AU - Gourdon, Pontus

AU - Davies, Michael J.

AU - Hägglund, Per

PY - 2020/9

Y1 - 2020/9

N2 - Anastellin (AN), a fragment of the first type III module in fibronectin (FN), initiates formation of superfibronectin, a polymer which resembles the native cell-derived fibrillar FN found in the extracellular matrix of many tissues, but which displays remarkably different functional properties. Here we demonstrate that exposure of AN to the biologically-important inflammatory oxidant, peroxynitrous acid (ONOOH), either as a bolus or formed at low levels in a time-dependent manner from SIN-1, impairs the capability of AN to polymerize FN. In contrast, exposure of FN to ONOOH does not seem to affect superfibronectin formation to the same extent. This oxidant-induced loss-of-function in AN occurs in a dose-dependent manner, and correlates with structural perturbations, loss of the amino acid tyrosine and tryptophan, and dose-dependent formation of modified amino acid side-chains (3-nitrotyrosine, di-tyrosine and 6-nitrotryptophan). Reagent ONOOH also induces formation of oligomeric species which decrease in the presence of bicarbonate, whereas SIN-1 mainly generates dimers. Modifications were detected at sub-stoichiometric (0.1-fold), or greater, molar excesses of oxidant compared to AN. These species have been localized to specific sites by peptide mass mapping. With high levels of oxidant (>100 times molar excess), ONOOH also induces unfolding of the beta-sheet structure of AN, thermal destabilization, and formation of high molecular mass aggregates. These results have important implications for the understanding of FN fibrillogenesis in vivo, and indicates that AN is highly sensitive to pathophysiological levels of oxidants such as ONOOH.

AB - Anastellin (AN), a fragment of the first type III module in fibronectin (FN), initiates formation of superfibronectin, a polymer which resembles the native cell-derived fibrillar FN found in the extracellular matrix of many tissues, but which displays remarkably different functional properties. Here we demonstrate that exposure of AN to the biologically-important inflammatory oxidant, peroxynitrous acid (ONOOH), either as a bolus or formed at low levels in a time-dependent manner from SIN-1, impairs the capability of AN to polymerize FN. In contrast, exposure of FN to ONOOH does not seem to affect superfibronectin formation to the same extent. This oxidant-induced loss-of-function in AN occurs in a dose-dependent manner, and correlates with structural perturbations, loss of the amino acid tyrosine and tryptophan, and dose-dependent formation of modified amino acid side-chains (3-nitrotyrosine, di-tyrosine and 6-nitrotryptophan). Reagent ONOOH also induces formation of oligomeric species which decrease in the presence of bicarbonate, whereas SIN-1 mainly generates dimers. Modifications were detected at sub-stoichiometric (0.1-fold), or greater, molar excesses of oxidant compared to AN. These species have been localized to specific sites by peptide mass mapping. With high levels of oxidant (>100 times molar excess), ONOOH also induces unfolding of the beta-sheet structure of AN, thermal destabilization, and formation of high molecular mass aggregates. These results have important implications for the understanding of FN fibrillogenesis in vivo, and indicates that AN is highly sensitive to pathophysiological levels of oxidants such as ONOOH.

KW - Aggregation

KW - Anastellin

KW - Extracellular matrix

KW - Fibronectin

KW - Peroxynitrous acid

KW - Protein oxidation

UR - http://www.scopus.com/inward/record.url?scp=85087816671&partnerID=8YFLogxK

U2 - 10.1016/j.redox.2020.101631

DO - 10.1016/j.redox.2020.101631

M3 - Journal article

C2 - 32807731

AN - SCOPUS:85087816671

SN - 2213-2317

VL - 36

JO - Redox Biology

JF - Redox Biology

M1 - 101631

ER -

Peroxynitrous acid (ONOOH) modifies the structure of anastellin and influences its capacity to polymerize fibronectin

Abstract

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