Effect of ginsenoside Rb1 on rat liver phosphoproteins induced by carbon tetrachloride.
We investigated the effects of ginsenoside Rb1 (G-Rb1), a major saponin from Panax ginseng C. A. MEYER, on rat liver protein phosphorylation after intraperitoneal administration of CCl4 alone or together with G-Rb1. We found that 118, 63, and 34kDa proteins were prominently phosphorylated in liver homogenates prepared from CCl4-administered rats, while these protein-phosphorylations were inhibited in the homogenate prepared from the G-Rb1 plus CCl4-administration group. When inhibitors of protein kinases were exogenously added to the homogenates from either the CCl4-administered group or the G-Rb1 plus CCl4-administered group, their phosphorylations were inhibited much more by W-7, an inhibitor of Ca2+/calmodulin-dependent protein kinase (CaM-PK), than by H-7, an inhibitor of protein kinase C (C-kinase). Interestingly, only 34kDa was phosphorylated in homogenates prepared from the corn oil-, G-Rb1-, and G-Rb1 plus CCl4-administered groups by the exogenous addition of sodium fluoride (NaF), an inhibitor of glycogen synthase. Additionally, G-Rb1 inhibited the Ca(2+)-accumulation induced by CCl4 both in liver homogenates and microsomes. The above results imply that G-Rb1 inhibits the CCl4-induced protein phosphorylations by modulating CaM-PK rather than C-kinase, and that 34kDa protein may play a different biological role in cellular environment from 118 and 63kDa proteins. Therefore, a study in which G-Rb1 is employed as a modulator of critical CCl4-induced phenomena ranging from the disturbance of Ca2+ concentration to protein phosphorylation may be successfully applicable to investigate the diverse physiological functions of liver.
Park
H J
HJ
Department of Biochemical Pharmacology, Korea Ginseng and Tobacco Research Institute, Taejon, Korea.
Park
K M
KM
Rhee
M H
MH
Song
Y B
YB
Choi
K J
KJ
Lee
J H
JH
Kim
S C
SC
Park
K H
KH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D036145:Ginsenosides; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008970:Molecular Weight; D005894:Panax; D010750:Phosphoproteins / Q000032:analysis*; D010766:Phosphorylation / Q000187:drug effects; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
D036145:Ginsenosides; D010750:Phosphoproteins; D012503:Saponins; D013449:Sulfonamides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006003:Glycogen; D002251:Carbon Tetrachloride; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium