Involvement of protein kinase C activation and cell survival/ cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action.
Studies from our laboratory have demonstrated that the major green tea polyphenol, (-)-epigallocatechin 3-gallate (EGCG), exerts potent neuroprotective actions in the mice model of Parkinson's disease. These studies were extended to neuronal cell culture employing the parkinsonism-inducing neurotoxin, 6-hydroxydopamine (6-OHDA). Pretreatment with EGCG (0.1-10 microm) attenuated human neuroblastoma (NB) SH-SY5Y cell death, induced by a 24-h exposure to 6-OHDA (50 microm). Potential cell signaling candidates involved in this neuroprotective effect were further examined. EGCG restored the reduced protein kinase C (PKC) and extracellular signal-regulated kinases (ERK1/2) activities caused by 6-OHDA toxicity. However, the neuroprotective effect of EGCG on cell survival was abolished by pretreatment with PKC inhibitor GF 109203X (1 microm). Because EGCG increased phosphorylated PKC, we suggest that PKC isoenzymes are involved in the neuroprotective action of EGCG against 6-OHDA. In addition, gene expression analysis revealed that EGCG prevented both the 6-OHDA-induced expression of several mRNAs, such as Bax, Bad, and Mdm2, and the decrease in Bcl-2, Bcl-w, and Bcl-x(L). These results suggest that the neuroprotective mechanism of EGCG against oxidative stress-induced cell death includes stimulation of PKC and modulation of cell survival/cell cycle genes.
Levites
Yona
Y
Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Dept. of Pharmacology, Technion-Faculty of Medicine, 31096 Haifa, Israel.
Amit
Tamar
T
Youdim
Moussa B H
MB
Mandel
Silvia
S
D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002453:Cell Cycle / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D004789:Enzyme Activation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D011493:Protein Kinase C / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D013662:Tea; D051028:bcl-2-Associated X Protein
D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013662:Tea; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D002392:Catechin; C045651:epigallocatechin gallate; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases