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Metab Brain Dis. 2019 Feb;34(1):61-69. doi: 10.1007/s11011-018-0319-y. Epub 2018 Sep 26.

Role of PUMA in the methamphetamine-induced migration of microglia.

Author information

1
Department of Pharmacology, Medical School of Southeast University, Southeast University, Nanjing, 210009, Jiangsu, China.
2
Department of Physiology, Medical School of Southeast University, Southeast University, Nanjing, China.
3
Key Laboratory for Zoonosis Research, Ministry of Education, Jilin University, Changchun, China.
4
Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
5
Department of Pathophysiology, Medical School of Southeast University, Southeast University, Nanjing, China.
6
Department of Pharmacology, Medical School of Southeast University, Southeast University, Nanjing, 210009, Jiangsu, China. yuanzhang@seu.edu.cn.

Abstract

In this study, we demonstrated that PUMA was involved in the microglial migration induced by methamphetamine. PUMA expression was examined by western blotting and immunofluorescence staining. BV2 and HAPI cells were pretreated with a sigma-1R antagonist and extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), c-Jun N-terminal protein kinase (JNK), and phosphatidylinositol-3 kinase (PI3K)/Akt inhibitors, and PUMA expression was detected by western blotting. The cell migration in BV2 and HAPI cells transfected with a lentivirus encoding red fluorescent protein (LV-RFP) was also examined using a wound-healing assay and nested matrix model and cell migration assay respectively. The molecular mechanisms of PUMA in microglial migration were validated using a siRNA approach. The exposure of BV2 and HAPI cells to methamphetamine increased the expression of PUMA, reactive oxygen species (ROS), the MAPK and PI3K/Akt pathways and the downstream transcription factor signal transducer and activator of transcription 3 (STAT3) pathways. PUMA knockdown in microglia transfected with PUMA siRNA attenuated the increased cell migration induced by methamphetamine, thereby implicating PUMA in the migration of BV2 and HAPI cells. This study demonstrated that methamphetamine-induced microglial migration involved PUMA up-regulation. Targeting PUMA could provide insights into the development of a potential therapeutic approach for the alleviation of microglia migration induced by methamphetamine.

KEYWORDS:

Methamphetamine; Microglia; Migration; PUMA

PMID:
30259295
DOI:
10.1007/s11011-018-0319-y
[Indexed for MEDLINE]

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