Our science


Peptide Inhibitor Of Complement C1 (PIC1) Demonstrates Antioxidant Activity Via Single Electron Transport (SET) And Hydrogen Atom Transfer (HAT)

PLoS One. 2018 Mar 2;13(3):e0193931. doi: 10.1371/journal.pone.0193931. eCollection 2018.


Reactive oxygen species (ROS) are natural byproducts of oxidative respiration that are toxic to organs and tissues. To mitigate ROS damage, organisms have evolved a variety of antioxidant systems to counteract these harmful molecules, however in certain pathological conditions these protective mechanisms can be overwhelmed. We have recently demonstrated that Peptide Inhibitor of Complement C1 (PIC1) mitigates peroxidase activity of the heme bearing proteins myeloperoxidase, hemoglobin, and myoglobin through a reversible process. To determine if this property of PIC1 was antioxidant in nature, we tested PIC1 in a number of well-established antioxidant assays. PIC1 showed dose-dependent antioxidant activity in a total antioxidant (TAC) assay, hydroxyl radical antioxidant capacity (HORAC) assay, oxygen radical antioxidant capacity (ORAC) assay as well as the thiobarbituric acid reactive substances (TBARS) assay to screen for PIC1 antioxidant activity in human plasma. The antioxidant activity of PIC1 in the TAC assay, as well as the HORAC/ORAC assay demonstrated that this peptide acts via the single electron transport (SET) and hydrogen atom transfer (HAT) mechanisms, respectively. Consistent with this mechanism of action, PIC1 did not show activity in a metal chelating activity (MCA) assay. PIC1 contains two vicinal cysteine residues and displayed similar antioxidant activity to the well characterized cysteine-containing tripeptide antioxidant molecule glutathione (GSH). Consistent with the role of the cysteine residues in the antioxidant activity of PIC1, oxidation of these residues significantly abrogated antioxidant activity. These results demonstrate that in addition to its described complement inhibiting activity, PIC1 displays in vitro antioxidant activity.

PMID: 29499069 PMCID: PMC5834197 DOI: 10.1371/journal.pone.0193931

More Abstracts

Aug 20, 2020

Incompatible Erythrocyte Transfusion With Lipopolysaccharide Induces Acute Lung Injury...

Acute transfusion reactions can manifest in many forms including acute hemolytic transfusion reaction, allergic reaction and transfusion-related...

Read More
Mar 28, 2018

Inhibition of Immune Complex Complement Activation And Neutrophil Extracellular...

Abstract: Two major aspects of systemic lupus erythematosus (SLE) pathogenesis that have yet to be targeted therapeutically are immune complex-i...

Read More
Dec 31, 2019

Inhibition of Complement Activation, Myeloperoxidase, NET Formation And Oxidant...

A product of rational molecular design, PA-dPEG24 is the lead derivative of the PIC1 family of peptides with multiple functional abilities inclu...

Read More