Acta pharmacologica Sinica, 2016-06, Vol.37 (6), p.731-740
2016
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- Autor(en) / Beteiligte
- Titel
- 20C, a bibenzyl compound isolated from Gastrodia elata, protects PC12 cells against rotenone-induced apoptosis via activation of the Nrf2/ARE/HO-1 signaling pathway
- Ist Teil von
- Acta pharmacologica Sinica, 2016-06, Vol.37 (6), p.731-740
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aim： Our preliminary study shows that a bibenzyl compound isolated from Gastrodia elata, 2-[4-hydroxy-3-（4-hydroxybenzyl）benzyl]-4-（4-hydroxybenzyl）phenol （designated 20C）, protects PC12 cells against H202-induced injury. In this study we investigated whether 20C exerted neuroprotective action in a cell model of Parkinson＇s disease. Methods： A cell model of Parkinson＇s disease was established in PC12 cells by exposure to rotenone （4 pmol/L） for 48 h. Cell viability and apoptosis were assessed, and intracellular ROS level and the mitochondrial membrane potential （MMP） were detected. The expression of apoptosis-related proteins Bax, Bcl-2, cytochrome c, cleaved caspase-3, and oxidative stress-related proteins Nrf2, HO-1 and NQ01 were examined using Western blotting. The mRNA levels of HO-1 and NQ01 were determined with RT-PCR. The nuclear translocation of Nrf2 was observed with immunofluorescence staining. Results： Treatment with rotenone significantly increased the number of apoptotic cells, accompanied by marked increases in the Bax/ Bcl-2 ratio, cytochrome c release and caspase-3 activation. Rotenone also increased ROS accumulation, reduced MMP, and increased the nuclear translocation of Nrf2 as well as the mRNA and protein levels of the Nrf2 downstream target genes HO-1 and NQ01 in PC12 cells. Co-treatment with 20C （0.01-1 pmol/L） dose-dependently attenuated rotenone-induced apoptosis and oxidative stress in PC12 cells. Nrf2 knockdown by siRNA partially reversed the protective effects of 20C in rotenone-treated PC12 cells. Conclusion： The bibenzyl compound 20C protects PC12 cells from rotenone-induced apoptosis, at least in part, via activation of the Nrf2/ARE/HO-1 signaling pathway.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1671-4083eISSN: 1745-7254DOI: 10.1038/aps.2015.154Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4954759
- Format
- –
- Schlagworte
- Animals, Antioxidant Response Elements - drug effects, Apoptosis - drug effects, Bibenzyls - chemistry, Bibenzyls - pharmacology, Biomedical and Life Sciences, Biomedicine, Gastrodia - chemistry, Gastrodia elata, Heme Oxygenase-1 - genetics, Heme Oxygenase-1 - metabolism, Immunology, Internal Medicine, Medical Microbiology, Neuroprotective Agents - chemistry, Neuroprotective Agents - pharmacology, NF-E2-Related Factor 2 - genetics, NF-E2-Related Factor 2 - metabolism, Original, original-article, Oxidative Stress - drug effects, Parkinson Disease, Secondary - drug therapy, Parkinson Disease, Secondary - genetics, Parkinson Disease, Secondary - metabolism, PC12 Cells, PC12细胞, Pharmacology/Toxicology, Rats, Reactive Oxygen Species - metabolism, RNA, Messenger - genetics, RNA, Small Interfering - genetics, Rotenone, Signal Transduction - drug effects, Vaccine, 信号通路, 神经保护作用, 类化合物, 细胞凋亡, 血红素加氧酶-1, 诱导, 鱼藤酮