Atrazine induces phagocytotic dysfunction of microglia depends on nucleocytoplasmic translocation of acetylated HMGB1

Ge Shi; Chunhui Zhang; Guoliang Li; Kaidong Wang; Qian Cai; Min Huang

Ecotoxicology and Environmental Safety (Mar 2023)

Atrazine induces phagocytotic dysfunction of microglia depends on nucleocytoplasmic translocation of acetylated HMGB1

Ge Shi,
Chunhui Zhang,
Guoliang Li,
Kaidong Wang,
Qian Cai,
Min Huang

Affiliations

Ge Shi: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China
Chunhui Zhang: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China
Guoliang Li: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China
Kaidong Wang: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China
Qian Cai: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Corresponding authors at: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China.
Min Huang: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China; Corresponding authors at: School of Public Health and Management, Ningxia Medical University, No.1160, the Street of Shengli, Xingqing District, Yinchuan, Ningxia, China.

Journal volume & issue: Vol. 252
p. 114583

Abstract

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Atrazine (ATR) is a widely applied herbicide which was named an environmental endocrine disrupting chemical (EDC). Increasing evidence indicates ATR causes neurotoxic effects resulting in central nervous system (CNS) disease. As the primary immunocytes in the CNS, microglia cells carry out their phagocytosis to maintain the CNS microenvironment by preventing damage from healthy cells. However, the mechanism in which ATR affects the phagocytic function of microglia remains unclear. The present study was designed to investigate the effect of ATR on the phagocytosis of microglia. BV-2 cells and primary microglia selected as microglial models in which BV-2 cells were administrated by ATR at different concentrations (0, 4, 8, 16 μM) for 24 h. Results demonstrated ATR dose-dependently increased the expression of ionized calcium binding adapter molecule 1 (Iba-1), indicating that microglia were activated. Microglial phagocytotic activity induced by ATR fluctuated at the different time points, accompanied by fluctuations in membrane receptor MERTK and cytoplasmic lysosomal marker LAMP1 (two markers related to cell phagocytosis). In this period, the expression of iNOS gradually increased. A mechanistic study further demonstrated that the translocation of High Mobility Group Protein-B1 (HMGB1) from nucleus to cytoplasm in the BV-2 and primary microglial cells induced by ATR, and the process showed a positive correlation with phagocytosis activity of BV-2 cells induced by ATR (r = 0.8030, P = 0.05; α = 0.1). ATR was also shown to spur the acetylation of HMGB1 by breaking the balance between acetylase P300 and deacetylase SIRT1. Unexpectedly, the inhibition of acetylating HMGB1 by resveratrol (Res) was effectively retained by HMGB1 in the nucleus, reversed the SIRT1 and MERTK expression, and enhanced the phagocytosis activity in BV-2 cells. Our results suggested that ATR exposure influenced microglial phagocytosis by acetylating HMGB1 further translocated it in the nucleoplasm.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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