A pro-drug of the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
| Autor: | Wai Hung Yuen, Wai Har Lam, Yuen Shan Ho, Cora Sau Wan Lai, Man-Shan Yu, Jianfei Chao, Way K.W. Lau, Tak Hang Chan, Raymond Chuen-Chung Chang, Michelle Justine Huie, Mingfu Wang |
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| Rok vydání: | 2010 |
| Předmět: |
Time Factors
SH-SY5Y Tretinoin Pharmacology Epigallocatechin gallate Neuroprotection Catechin chemistry.chemical_compound Cell Line Tumor Humans Phosphorylation Oxidopamine Protein kinase B Neurons Hydroxydopamine Dose-Response Relationship Drug L-Lactate Dehydrogenase Caspase 3 Chemistry General Neuroscience Parkinson Disease Biological activity Bioavailability Neuroprotective Agents Biochemistry Proto-Oncogene Proteins c-akt Central Nervous System Agents Signal Transduction |
| Zdroj: | Neuroscience Letters. 469:360-364 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2009.12.028 |
| Popis: | Regular consumption of green tea benefits people in prevention from cardiovascular disorders, obesity as well as neurodegenerative diseases. (-)-Epigallocatechin-3-gallate (EGCG) is regarded as the most biologically active catechin in green tea. However, the stability and bioavailability of EGCG are restricted. The purpose of the present study was to investigate whether a pro-drug, a fully acetylated EGCG (pEGCG), could be more effective in neuroprotection in Parkinsonism mimic cellular model. Retinoic acid (RA)-differentiated neuroblastoma SH-SY5Y cells were pre-treated with different concentrations of EGCG and pEGCG for 30 min and followed by incubation of 25 microM 6-hydroxydopamine (6-OHDA) for 24h. We found that a broad dosage range of pEGCG (from 0.1 to 10 microM) could significantly reduce lactate dehydrogenase release. Likewise, 10 microM of pEGCG was effective in reducing caspase-3 activity, while EGCG at all concentrations tested in the model failed to attenuate caspase-3 activity induced by 6-OHDA. Furthermore, Western-blot analysis showed that Akt could be one of the specific signaling pathways stimulated by pEGCG in neuroprotection. It was demonstrated that 25 microM of 6-OHDA significantly suppressed the phosphorylation level of Akt. Only pEGCG at 10 microM markedly increased its phosphorylation level compared to 6-OHDA alone. Taken together, as pEGCG has higher stability and bioavailability for further investigation, it could be a potential neuroprotective agent and our current findings may offer certain clues for optimizing its application in future. |
| Databáze: | OpenAIRE |
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