Phospholipase C, protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and redox state are involved in epigallocatechin gallate-induced phospholipase D activation in human astroglioma cells.
We show that epigallocatechin-3 gallate (EGCG), a major component of green tea, stimulates phospholipase D (PLD) activity in U87 human astroglioma cells. EGCG-induced PLD activation was abolished by the phospholipase C (PLC) inhibitor and a lipase inactive PLC-gamma1 mutant, which is dependent on intracellular or extracellular Ca(2+), with the possible involvement of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II). EGCG induced translocation of PLC-gamma1 from the cytosol to the membrane and PLC-gamma1 interaction with PLD1. EGCG regulates the activity of PLD by modulating the redox state of the cells, and antioxidants reverse this effect. Moreover, EGCG-induced PLD activation was reduced by PKC inhibitors or down-regulation of PKC. Taken together, these results show that, in human astroglioma cells, EGCG regulates PLD activity via a signaling pathway involving changes in the redox state that stimulates a PLC-gamma1 [Ins(1,4,5)P(3)-Ca(2+)]-CaM kinase II-PLD pathway and a PLC-gamma1 (diacylglycerol)-PKC-PLD pathway.
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Shi Yeon
SY
Kim
Bong-Hyun
BH
Ahn
Joonmo
J
Kim
Yoe-Sik
YS
Bae
Jong-Young
JY
Kwak
Gyesik
G
Min
Taeg Kyu
TK
Kwon
Jong-Soo
JS
Chang
Young Han
YH
Lee
Shin-Hee
SH
Yoon
Do Sik
DS
Min
D000970:Antineoplastic Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D051966:Phospholipase C gamma; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013662:Tea / Q000737:chemistry; D010738:Type C Phospholipases / Q000378:metabolism*
D000970:Antineoplastic Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D010739:Phospholipase D; C106801:phospholipase D1; D002118:Calcium