Downregulated Recycling Process but Not De Novo Synthesis of Glutathione Limits Antioxidant Capacity of Erythrocytes in Hypoxia

Author:

Wang Yueming1ORCID,Zhao Nannan2ORCID,Xiong Yanlei3ORCID,Zhang Jiashen2ORCID,Zhao Dongmei1ORCID,Yin Yancun1ORCID,Song Lele2ORCID,Yin Yipeng2ORCID,Wang Jing2ORCID,Luan Xiying2ORCID,Xiong Yanlian1ORCID

Affiliation:

1. Department of Anatomy, School of Basic Medicine, Binzhou Medical University, Yantai, China

2. Department of Immunology, School of Basic Medicine, Binzhou Medical University, Yantai, China

3. Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China

Abstract

Red blood cells (RBCs) are susceptible to sustained free radical damage during circulation, while the changes of antioxidant capacity and regulatory mechanism of RBCs under different oxygen gradients remain unclear. Here, we investigated the changes of oxidative damage and antioxidant capacity of RBCs in different oxygen gradients and identified the underlying mechanisms using an in vitro model of the hypoxanthine/xanthine oxidase (HX/XO) system. In the present study, we reported that the hypoxic RBCs showed much higher oxidative stress injury and lower antioxidant capacity compared with normoxic RBCs. In addition, we found that the disturbance of the recycling process, but not de novo synthesis of glutathione (GSH), accounted for the significantly decreased antioxidant capacity of hypoxic RBCs compared to normoxic RBCs. We further elucidated the underlying molecular mechanism by which oxidative phosphorylation of Band 3 blocked the hexose monophosphate pathway (HMP) and decreased NADPH production aggravating the dysfunction of GSH synthesis in hypoxic RBCs under oxidative conditions.

Funder

National Undergraduate Innovation and Entrepreneurship Training Program

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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