Iodide modulates protein damage induced by the inflammation-associated heme enzyme myeloperoxidase

Abstract

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.

Elevated levels of iodide promote peroxidase-mediated protein iodination and inhibit protein chlorination

“…5). This is consistent with previous data with fibronectin where a protective effect of I⁻ against dimerization was observed [11]. Furthermore, the absence of dimer formation induced by LPO/H₂O₂/I⁻ (and inhibition of MPO-mediated oligomerization) is consistent with an absence of I • , as many cross-linking processes involve radical-radical reactions [55].…”

Comprehensive Molecular Study Reveals the Potential Role of Chebulinic Acid and Boeravinone B to Establish Redox Homeostasis in Metabolically Stressed Cells

“…Our study coincides with previous work that suggests supplementation with iodine ions (can be applied within a 0.1-10 μM range by oral supplementation in humans) can lower damage to proteins and cellular components by modulating oxidative protein damage caused by the inflammation-associated heme enzyme myeloperoxidase [45].…”

Chronic cardiac structural damage, diastolic and systolic dysfunction following acute myocardial injury due to bromine exposure in rats

“…Further inactivation of SERCA derives from molecular modifications, such as bromination generating Br-SERCA, which in this case is increased when corrected by total SERCA in animals 28 days after exposure. Although, we did not find measurable amounts of brominated fatty acids in cardiac tissues in delayed samples the halogenation of SERCA at this later time point could be caused by a later accumulation of other brominated moieties or from the hypochlorous or hypobromous acids (HOCl or HOBr) formed by myeloperoxidase activity in vivo 47,48 .…”