(-)-Epigallocatechin-3-Gallate protects SH-SY5Y cells against 6-OHDA-induced cell death through STAT3 activation.
As a natural product, (-)-Epigallocatechin-3-gallate (EGCG), has demonstrated remarkable neuronal protection by depressing oxidative stress in Parkinson's disease (PD). However, the molecular mechanisms underlying EGCG neuronal protection have not been clarified. Using 6-hydroxydopamine (6-OHDA)-treated human neuroblastoma SH-SY5Y cells as a PD cell model, we found that 6-OHDA can cause neuronal death by regulating the activity of STAT3. Pretreatment of SH-SY5Y cells with EGCG (0.1-10 microM) significantly attenuated cell death induced by 6-OHDA. In addition, STAT3 activity decline induced by 6-OHDA in SH-SY5Y cells can be completely prevented by the presence of 1 microM of EGCG, and neuronal cell proliferation can be stimulated by EGCG treatment. These results clearly demonstrate that the disruption of STAT3 signaling by 6-OHDA makes significant contribution to the neuronal death in PD, and the protection of EGCG on neurons against oxidative stress-induced cell death may result from the re-stimulation of STAT3 signaling pathway. Our study not only clarified the role of STAT3 signaling pathway in oxidative stress-induced neuronal cell death, but also identified its involvement in the protection mechanism of EGCG on neurons in PD. The data resulting from our study also suggest that STAT3 may serve as a potential therapeutic target for drug development in PD.
Wang
Lili
L
Department of Neurology and Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China. bitljq@sohu.com
Xu
Shengli
S
Xu
Xianhao
X
Chan
Piu
P
D018663:Adrenergic Agents / Q000494:pharmacology*; D000704:Analysis of Variance; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D018663:Adrenergic Agents; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; D014316:Tritium; D014443:Tyrosine; D016627:Oxidopamine; D002392:Catechin; C045651:epigallocatechin gallate; C022616:thiazolyl blue; D013936:Thymidine