Histidine-rich glycoprotein possesses antioxidant activity through self-oxidation and inhibition of hydroxyl radical production via chelating divalent metal ions in Fenton's reaction.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 9423872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1029-2470 (Electronic) Linking ISSN: 10292470 NLM ISO Abbreviation: Free Radic Res Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: Yverdon, Switzerland : New York, NY : Harwood Academic ; distributed by STBS Ltd., c1994-

Antioxidants/*chemistry ; Cations, Divalent/*chemistry ; Glycoproteins/*chemistry ; Hydrogen Peroxide/*chemistry ; Hydroxyl Radical/*chemistry ; Iron/*chemistry ; Proteins/*chemistry ; Sepsis/*genetics; Humans ; Oxidation-Reduction ; Sepsis/pathology

Sepsis is caused by infections associated with life-threatening multiple organ failure (MOF). Septic MOF appears to be closely related to circulatory failure due to immunothrombosis. This process involves the production of reactive oxygen spices (ROS) in inflammatory sites. Therefore, the detoxification of the systemic excess ROS is important for the improvement of the process in septic pathogenesis. Histidine-rich glycoprotein (HRG), a plasma glycoprotein, ameliorates a septic condition through the suppression of both excess ROS production from neutrophils and immunothrombosis. Hydroxyl radical is known as the most important species among ROS in pathogenesis; however, the direct influence of HRG on hydroxyl radical formation and ROS activity is poorly understood. In this study, we showed that HRG, in a concentration-dependent manner, efficiently inhibited the production of hydroxyl radical induced by the Fenton's reaction through chelation of the divalent iron. HRG also exhibited antioxidant activity against peroxyl radical by oxidation of HRG itself as a substrate; however, it did not show superoxide dismutase and catalase-like activities. Additionally, HRG enhanced glutathione peroxidase, a well-known antioxidant enzyme, activity. These results suggest that HRG may play a unique role in suppression of the production of hydroxyl radicals and subsequent tissue damage at inflammatory sites. Marked reduction in plasma HRG in sepsis might lose such an important protective mechanism. Thus, the present study provides evidence that inhibition of ROS and ROS-production systems by HRG may contribute to antiseptic effects in vivo and that HRG could be potential therapy for ROS-related diseases.

Keywords: Fenton’s reaction; Histidine-rich glycoprotein; divalent metal ions; reactive oxygen spices; sepsis

0 (Antioxidants)
0 (Cations, Divalent)
0 (Fenton's reagent)
0 (Glycoproteins)
0 (Proteins)
0 (histidine-rich proteins)
3352-57-6 (Hydroxyl Radical)
BBX060AN9V (Hydrogen Peroxide)
E1UOL152H7 (Iron)

Date Created: 20200924 Date Completed: 20210804 Latest Revision: 20210804

20221213

10.1080/10715762.2020.1825703

32967483