Role of high-mobility group box 1 in methamphetamine-induced activation and migration of astrocytes

About the author

Dr. Honghong Yao, Professor at the Southeast University, Department of Pharmacology. Dr. Yao considered to be an international expert in the field of neuroscience. As such, she has published extensively in academic, peer-reviewed journals and am a frequent invitee and speaker at international conferences and various research institutions and universities within the US, Europe, and other parts of the world. In addition, she has received a $3 million Medical Research Council group grant; have served on numerous national and international committees; and have received numerous scholastic honors and awards.

Journal Reference

J Neuroinflammation. 2015;12:156.

Zhang Y¹, Zhu T², Zhang X¹, Chao J³, Hu G⁴, Yao H^5,6.

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Department of Pharmacology, Medical School of Southeast University, Nanjing, 210009, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Department of Physiology, Medical School of Southeast University, Nanjing, China.
Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Department of Pharmacology, Medical School of Southeast University, Nanjing, 210009, China. [email protected].
Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, China. [email protected].

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Abstract

BACKGROUND:

Mounting evidence has indicated that high-mobility group box 1 (HMGB1) is involved in cell activation and migration. Our previous study demonstrated that methamphetamine mediates activation of astrocytes via sigma-1 receptor (σ-1R). However, the elements downstream of σ-1R in this process remain poorly understood. Thus, we examined the molecular mechanisms involved in astrocyte activation and migration induced by methamphetamine.

METHODS:

The expression of HMGB1, σ-1R, and glial fibrillary acidic protein (GFAP) was examined by western blot and immunofluorescent staining. The phosphorylation of cell signaling pathways was detected by western blot, and cell migration was examined using a wound-healing assay in rat C6 astroglia-like cells transfected with lentivirus containing red fluorescent protein (LV-RFP) as well as in primary human astrocytes. The role of HMGB1 in astrocyte activation and migration was validated using a siRNA approach.

RESULTS:

Exposure of C6 cells to methamphetamine increased the expression of HMGB1 via the activation of σ-1R, Src, ERK mitogen-activated protein kinase, and downstream NF-κB p65 pathways. Moreover, methamphetamine treatment resulted in increased cell activation and migration in C6 cells and primary human astrocytes. Knockdown of HMGB1 in astrocytes transfected with HMGB1 siRNA attenuated the increased cell activation and migration induced by methamphetamine, thereby implicating the role of HMGB1 in the activation and migration of C6 cells and primary human astrocytes.

CONCLUSIONS:

This study demonstrated that methamphetamine-mediated activation and migration of astrocytes involved HMGB1 up-regulation through an autocrine mechanism. Targeting HMGB1 could provide insights into the development of a potential therapeutic approach for alleviation of cell activation and migration of astrocytes induced by methamphetamine.

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