Role of PUMA in methamphetamine-induced neuronal apoptosis.

Chuanxiang Chen, Litao Qincao, Jingtao Xu, Sihao Du, Enping Huang, Chao Liu, Zhoumeng Lin, Wei-Bing Xie, Huijun Wang

Toxicology letters 2016 Jan 5

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Exposure to methamphetamine (METH), a widely used illicit drug, has been shown to cause neuron apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a key mediator in neuronal apoptosis. This study aimed to examine the effects of PUMA in METH-induced neuronal apoptosis. We determined PUMA protein expression in PC12 cells and SH-SY5Y cells after METH exposure using western blot. We also observed the effect of METH on neuronal apoptosis after silencing PUMA expression with siRNA using TUNEL staining and flow cytometry. Additionally, to investigate possible mechanisms of METH-induced PUMA-mediated neuronal apoptosis, we measured the protein expression of apoptotic markers, including cleaved caspase-3, cleaved PARP, Bax, B-cell leukemia/lymphoma-2 (Bcl-2) and cytochrome c (cyto c), after METH treatment with or without PUMA knockdown. Results showed that METH exposure induced cell apoptosis, increased PUMA protein levels, activated caspase-3 and PARP, elevated Bax and reduced Bcl-2 expression, as well as increased the release of cyto c from mitochondria to the cytoplasm in both PC12 and SH-SY5Y cells. All these effects were attenuated or reversed after silencing PUMA. A schematic depicting the role of PUMA in METH-induced mitochondrial apoptotic pathway was proposed. Our results suggest that PUMA plays an important role in METH-triggered apoptosis and it may be a potential target for ameliorating neuronal injury and apoptosis caused by METH. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Citation

Chuanxiang Chen, Litao Qincao, Jingtao Xu, Sihao Du, Enping Huang, Chao Liu, Zhoumeng Lin, Wei-Bing Xie, Huijun Wang. Role of PUMA in methamphetamine-induced neuronal apoptosis. Toxicology letters. 2016 Jan 5;240(1):149-60