Yohei Takahashi
   Department   Kawasaki University of Medical Welfare  ,
   Position   Instructor
Article types 原著
Language English
Peer review Peer reviewed
Title Histidine-rich glycoprotein possesses antioxidant activity through self-oxidation and inhibition of hydroxyl radical production via chelating divalent metal ions in Fenton's reaction.
Journal Formal name:Free radical research
Abbreviation:Free Radic Res
ISSN code:10292470/10292470
Domestic / ForeginForegin
Volume, Issue, Page 54(8-9),pp.649-661
Author and coauthor Hidenori Wake, Yohei Takahashi, Yukinori Yoshii, Shangze Gao, Shuji Mori, Dengli Wang, Kiyoshi Teshigawara, Masahiro Nishibori
Publication date 2020/09
Summary 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.
DOI 10.1080/10715762.2020.1825703
PMID 32967483