Role of PUMA in the methamphetamine-induced migration of microglia
- 112 Downloads
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.
KeywordsPUMA Methamphetamine Microglia Migration
This work was supported by grants from the National Natural Science Foundation of China (No. 81322048 and No. 81473190).
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
- Cregan SP, Arbour NA, Maclaurin JG, Callaghan SM, Fortin A, Cheung EC, Guberman DS, Park DS, Slack RS (2004) p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death. J Neurosci Off J Soc Neurosci 24:10003–10012. https://doi.org/10.1523/jneurosci.2114-04.2004 CrossRefGoogle Scholar
- Gonzalez B, Raineri M, Cadet JL, Garcia-Rill E, Urbano FJ, Bisagno V (2014) Modafinil improves methamphetamine-induced object recognition deficits and restores prefrontal cortex ERK signaling in mice. Neuropharmacology 87:188–197. https://doi.org/10.1016/j.neuropharm.2014.02.002 CrossRefPubMedPubMedCentralGoogle Scholar
- Li X, Liu S, Luo J, Liu A, Tang S, Liu S, Yu M, Zhang Y (2015) Helicobacter pylori induces IL-1beta and IL-18 production in human monocytic cell line through activation of NLRP3 inflammasome via ROS signaling pathway. Pathog Dis 73. https://doi.org/10.1093/femspd/ftu024
- Liu S, Mi WL, Li Q, Zhang MT, Han P, Hu S, Mao-Ying QL, Wang YQ (2015) Spinal IL-33/ST2 signaling contributes to neuropathic pain via neuronal CaMKII-CREB and Astroglial JAK2-STAT3 cascades in mice. Anesthesiology 123:1154–1169. https://doi.org/10.1097/aln.0000000000000850 CrossRefPubMedGoogle Scholar
- Ma J, Wan J, Meng J, Banerjee S, Ramakrishnan S, Roy S (2014) Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the kappa opioid receptor. Cell Death Dis 5:e1099. https://doi.org/10.1038/cddis.2014.64 CrossRefPubMedPubMedCentralGoogle Scholar
- Seminerio MJ, Robson MJ, McCurdy CR, Matsumoto RR (2012) Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1beta mRNA expression in the hypothalamus. Eur J Pharmacol 691:103–109. https://doi.org/10.1016/j.ejphar.2012.07.029 CrossRefPubMedPubMedCentralGoogle Scholar
- Shin EJ, Shin SW, Nguyen TTL, Park DH, Wie MB, Jang CG, Nah SY, Yang BW, Ko SK, Nabeshima T, Kim HC (2014) Ginsenoside re rescues methamphetamine-induced oxidative damage, mitochondrial dysfunction, microglial activation, and dopaminergic degeneration by inhibiting the protein kinase Cdelta gene. Mol Neurobiol 49:1400–1421. https://doi.org/10.1007/s12035-013-8617-1 CrossRefPubMedGoogle Scholar
- Vavrova J, Rezacova M (2014) Importance of proapoptotic protein PUMA in cell radioresistance. Folia Biol 60:53–56Google Scholar
- Yao H, Yang Y, Kim KJ, Bethel-Brown C, Gong N, Funa K, Gendelman HE, Su TP, Wang JQ, Buch S (2010) Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration. Blood 115:4951–4962. https://doi.org/10.1182/blood-2010-01-266221 CrossRefPubMedPubMedCentralGoogle Scholar
- Zhang Y, Lv X, Bai Y, Zhu X, Wu X, Chao J, Duan M, Buch S, Chen L, Yao H (2015) Involvement of sigma-1 receptor in astrocyte activation induced by methamphetamine via up-regulation of its own expression. J Neuroinflammation 12:29. https://doi.org/10.1186/s12974-015-0250-7 CrossRefPubMedPubMedCentralGoogle Scholar