Iodide modulates protein damage induced by the inflammation-associated heme enzyme myeloperoxidase
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Iodide modulates protein damage induced by the inflammation-associated heme enzyme myeloperoxidase. / Gamon, Luke F.; Dieterich, Simon; Ignasiak, Marta T.; Schrameyer, Verena; Davies, Michael J.
I: Redox Biology, Bind 28, 101331, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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T1 - Iodide modulates protein damage induced by the inflammation-associated heme enzyme myeloperoxidase
AU - Gamon, Luke F.
AU - Dieterich, Simon
AU - Ignasiak, Marta T.
AU - Schrameyer, Verena
AU - Davies, Michael J.
PY - 2020
Y1 - 2020
N2 - Iodide ions (I−) are an essential dietary mineral, and crucial for mental and physical development, fertility and thyroid function. I− is also a high affinity substrate for the heme enzyme myeloperoxidase (MPO), which is involved in bacterial cell killing during the immune response, and also host tissue damage during inflammation. In the presence of H2O2 and Cl−, MPO generates the powerful oxidant hypochlorous acid (HOCl), with excessive formation of this species linked to multiple inflammatory diseases. In this study, we have examined the hypothesis that elevated levels of I− would decrease HOCl formation and thereby protein damage induced by a MPO/Cl−/H2O2 system, by acting as a competitive substrate. The presence of increasing I− concentrations (0.1–10 μM; i.e. within the range readily achievable by oral supplementation in humans), decreased damage to both model proteins and extracellular matrix components as assessed by gross structural changes (SDS-PAGE), antibody recognition of parent and modified protein epitopes (ELISA), and quantification of both parent amino acid loss (UPLC) and formation of the HOCl-biomarker 3-chlorotyrosine (LC-MS) (reduced by ca. 50% at 10 μM I−). Elevated levels of I− ( > 1 μM) also protected against functional changes as assessed by a decreased loss of adhesion (eg. 40% vs. < 22% with >1 μM I−) of primary human coronary artery endothelial cells (HCAECs), to MPO-modified human plasma fibronectin. These data indicate that low micromolar concentrations of I−, which can be readily achieved in humans and are readily tolerated, may afford protection against cell and tissue damage induced by MPO.
AB - Iodide ions (I−) are an essential dietary mineral, and crucial for mental and physical development, fertility and thyroid function. I− is also a high affinity substrate for the heme enzyme myeloperoxidase (MPO), which is involved in bacterial cell killing during the immune response, and also host tissue damage during inflammation. In the presence of H2O2 and Cl−, MPO generates the powerful oxidant hypochlorous acid (HOCl), with excessive formation of this species linked to multiple inflammatory diseases. In this study, we have examined the hypothesis that elevated levels of I− would decrease HOCl formation and thereby protein damage induced by a MPO/Cl−/H2O2 system, by acting as a competitive substrate. The presence of increasing I− concentrations (0.1–10 μM; i.e. within the range readily achievable by oral supplementation in humans), decreased damage to both model proteins and extracellular matrix components as assessed by gross structural changes (SDS-PAGE), antibody recognition of parent and modified protein epitopes (ELISA), and quantification of both parent amino acid loss (UPLC) and formation of the HOCl-biomarker 3-chlorotyrosine (LC-MS) (reduced by ca. 50% at 10 μM I−). Elevated levels of I− ( > 1 μM) also protected against functional changes as assessed by a decreased loss of adhesion (eg. 40% vs. < 22% with >1 μM I−) of primary human coronary artery endothelial cells (HCAECs), to MPO-modified human plasma fibronectin. These data indicate that low micromolar concentrations of I−, which can be readily achieved in humans and are readily tolerated, may afford protection against cell and tissue damage induced by MPO.
KW - 3-Chlorotyrosine
KW - Fibronectin
KW - Hypochlorous acid
KW - Inflammation
KW - Iodide
KW - Myeloperoxidase
U2 - 10.1016/j.redox.2019.101331
DO - 10.1016/j.redox.2019.101331
M3 - Journal article
C2 - 31568923
AN - SCOPUS:85072645338
VL - 28
JO - Redox Biology
JF - Redox Biology
SN - 2213-2317
M1 - 101331
ER -
ID: 228207065