Role of PUMA in methamphetamine-induced neuronal apoptosis
| Autor: | Jingtao Xu, Si-Hao Du, Chuanxiang Chen, Zhoumeng Lin, Huijun Wang, Enping Huang, Wei-Bing Xie, Chao Liu, Litao Qincao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytoplasm Down-Regulation Apoptosis Caspase 3 Toxicology PC12 Cells Methamphetamine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bcl-2-associated X protein Cell Line Tumor Proto-Oncogene Proteins hemic and lymphatic diseases Puma In Situ Nick-End Labeling Animals Humans p53 upregulated modulator of apoptosis Gene Silencing RNA Small Interfering bcl-2-Associated X Protein Neurons TUNEL assay biology Cytochrome c Cytochromes c General Medicine Meth biology.organism_classification Mitochondria Rats Up-Regulation Cell biology 030104 developmental biology chemistry biology.protein biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins 030217 neurology & neurosurgery |
| Zdroj: | Toxicology Letters. 240:149-160 |
| ISSN: | 0378-4274 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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