Exposure to peroxynitrite impacts the ability of anastellin to modulate the structure of extracellular matrix
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Exposure to peroxynitrite impacts the ability of anastellin to modulate the structure of extracellular matrix. / He, Jianfei; Chuang, Christine Y.; Hawkins, Clare L.; Davies, Michael J.; Hägglund, Per.
In: Free Radical Biology and Medicine, Vol. 206, 2023, p. 83-93.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Exposure to peroxynitrite impacts the ability of anastellin to modulate the structure of extracellular matrix
AU - He, Jianfei
AU - Chuang, Christine Y.
AU - Hawkins, Clare L.
AU - Davies, Michael J.
AU - Hägglund, Per
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - The extracellular matrix (ECM) of tissues consists of multiple proteins, proteoglycans and glycosaminoglycans that form a 3-dimensional meshwork structure. This ECM is exposed to oxidants including peroxynitrite (ONOO−/ONOOH) generated by activated leukocytes at sites of inflammation. Fibronectin, a major ECM protein targeted by peroxynitrite, self-assembles into fibrils in a cell-dependent process. Fibrillation of fibronectin can also be initiated in a cell-independent process in vitro by anastellin, a recombinant fragment of the first type-III module in fibronectin. Previous studies demonstrated that modification of anastellin by peroxynitrite impairs its fibronectin polymerization activity. We hypothesized that exposure of anastellin to peroxynitrite would also impact on the structure of ECM from cells co-incubated with anastellin, and influence interactions with cell surface receptors. Fibronectin fibrils in the ECM of primary human coronary artery smooth muscle cells exposed to native anastellin are diminished, an effect which is reversed to a significant extent by pre-incubation of anastellin with high (200-fold molar excess) concentrations of peroxynitrite. Treatment with low or moderate levels of peroxynitrite (2–20 fold molar excess) influences interactions between anastellin and heparin polysaccharides, as a model of cell-surface proteoglycan receptors, and modulates anastellin-mediated alterations in fibronectin cell adhesiveness. Based on these observations it is concluded that peroxynitrite has a dose-dependent influence on the ability of anastellin to modulate ECM structure via interactions with fibronectin and other cellular components. These observations may have pathological implications since alterations in fibronectin processing and deposition have been associated with several pathologies, including atherosclerosis.
AB - The extracellular matrix (ECM) of tissues consists of multiple proteins, proteoglycans and glycosaminoglycans that form a 3-dimensional meshwork structure. This ECM is exposed to oxidants including peroxynitrite (ONOO−/ONOOH) generated by activated leukocytes at sites of inflammation. Fibronectin, a major ECM protein targeted by peroxynitrite, self-assembles into fibrils in a cell-dependent process. Fibrillation of fibronectin can also be initiated in a cell-independent process in vitro by anastellin, a recombinant fragment of the first type-III module in fibronectin. Previous studies demonstrated that modification of anastellin by peroxynitrite impairs its fibronectin polymerization activity. We hypothesized that exposure of anastellin to peroxynitrite would also impact on the structure of ECM from cells co-incubated with anastellin, and influence interactions with cell surface receptors. Fibronectin fibrils in the ECM of primary human coronary artery smooth muscle cells exposed to native anastellin are diminished, an effect which is reversed to a significant extent by pre-incubation of anastellin with high (200-fold molar excess) concentrations of peroxynitrite. Treatment with low or moderate levels of peroxynitrite (2–20 fold molar excess) influences interactions between anastellin and heparin polysaccharides, as a model of cell-surface proteoglycan receptors, and modulates anastellin-mediated alterations in fibronectin cell adhesiveness. Based on these observations it is concluded that peroxynitrite has a dose-dependent influence on the ability of anastellin to modulate ECM structure via interactions with fibronectin and other cellular components. These observations may have pathological implications since alterations in fibronectin processing and deposition have been associated with several pathologies, including atherosclerosis.
KW - Cell adhesion
KW - Extracellular matrix
KW - Fibronectin
KW - Matrix assembly
KW - Nitration
KW - Peroxynitrite
KW - Protein oxidation
UR - http://www.scopus.com/inward/record.url?scp=85163417871&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2023.06.028
DO - 10.1016/j.freeradbiomed.2023.06.028
M3 - Journal article
C2 - 37385567
AN - SCOPUS:85163417871
VL - 206
SP - 83
EP - 93
JO - Free Radical Biology & Medicine
JF - Free Radical Biology & Medicine
SN - 0891-5849
ER -
ID: 360067121