Milk Fat Globule-Epidermal Growth Factor-Factor 8 Reverses Lipopolysaccharide-Induced Microglial Oxidative Stress

Author:

Li Jie1,Xu Xiaotian2,Cai Xiaoying3,Weng Yinlun4,Wang Yiping5,Shen Qingyu1,Shi Xiaolei6ORCID

Affiliation:

1. Department of Neurology, Zengcheng District People’s Hospital of Guangzhou, Guangzhou, China

2. Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

3. Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4. Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Guangzhou, China

5. Department of Neurosurgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China

6. Department of Neurology, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, China

Abstract

Oxidative stress plays an important role in various neurological disorders. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) is a regulatory protein for microglia. However, its involvement in microglial oxidative stress has not been established. In this study, we observed microglial oxidative stress in response to lipopolysaccharide (LPS) both in vitro and in vivo. LPS induced significant elevation of TNF-α, IL-6, MDA, and ROS and reduction of GSH and SOD in the mouse brains and primary microglia, which were reversed by MFG-E8 pretreatment. MFG-E8 induced the expression of Nrf-2 and HO-1 that was reduced by LPS incubation. Moreover, LPS-increased Keap-1 expression was reversed by MFG-E8. But the above tendencies were not seen when MFG-E8 was applied alone. The current study established the involvement of MFG-E8 in antioxidant effects during neuroinflammation. It may achieve the effects through the regulation of Keap-1/Nrf-2/HO-1 pathways.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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