Peptide Inhibitor of Complement C1 (PIC1) demonstrates antioxidant activity via
single electron transport (SET) and hydrogen atom transfer (HAT)
#MMPMID29499069
Gregory Rivera M
; Hair PS
; Cunnion KM
; Krishna NK
PLoS One
2018[]; 13
(3
): e0193931
PMID29499069
show ga
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.
free
free
free
