Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5′monophosphate kinase: A study in vitro and in vivo

Life Sciences ◽  
2015 ◽  
Vol 139 ◽  
pp. 8-15 ◽  
Author(s):  
Shengnan Wei ◽  
Wei Li ◽  
Yang Yu ◽  
Fan Yao ◽  
Lixiang A ◽  
...  
Keyword(s):  
Compound K ◽  
Hepatic Gluconeogenesis ◽  
Ginsenoside Compound K ◽  
Kinase A

scholarly journals Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo

2019 ◽  
Vol 20 (17) ◽  
pp. 4279 ◽  
Author(s):  
Jung-Mi Oh ◽  
Eunhee Kim ◽  
Sungkun Chun
Keyword(s):  
Cell Death ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Autophagic Flux ◽  
Ros Scavenging ◽  
Compound K ◽  
Human Neuroblastoma ◽  
Ginsenoside Compound K

Autophagy can result in cellular adaptation, as well as cell survival or cell death. Modulation of autophagy is increasingly regarded as a promising cancer therapeutic approach. Ginsenoside compound K (CK), an active metabolite of ginsenosides isolated from Panax ginseng C.A. Meyer, has been identified to inhibit growth of cancer cell lines. However, the molecular mechanisms of CK effects on autophagy and neuroblastoma cell death have not yet been investigated. In the present study, CK inhibited neuroblastoma cell proliferation in vitro and in vivo. Treatment by CK also induced the accumulation of sub-G1 population, and caspase-dependent apoptosis in neuroblastoma cells. In addition, CK promotes autophagosome accumulation by inducing early-stage autophagy but inhibits autophagic flux by blocking of autophagosome and lysosome fusion, the step of late-stage autophagy. This effect of CK appears to be mediated through the induction of intracellular reactive oxygen species (ROS) and mitochondria membrane potential loss. Moreover, chloroquine, an autophagy flux inhibitor, further promoted CK-induced apoptosis, mitochondrial ROS induction, and mitochondria damage. Interestingly, those promoted phenomena were rescued by co-treatment with a ROS scavenging agent and an autophagy inducer. Taken together, our findings suggest that ginsenoside CK induced ROS-mediated apoptosis and autophagic flux inhibition, and the combination of CK with chloroquine, a pharmacological inhibitor of autophagy, may be a novel therapeutic potential for the treatment of neuroblastoma.

Octyl ester of ginsenoside compound K as novel anti-hepatoma compound: Synthesis and evaluation on murine H22 cells in vitro and in vivo

2017 ◽  
Vol 91 (4) ◽  
pp. 951-956 ◽  
Author(s):  
Jingang Hou ◽  
Jianjie Xue ◽  
Xinghua Zhao ◽  
Zi Wang ◽  
Wei Li ◽  
...  
Keyword(s):  
Compound K ◽  
Compound Synthesis ◽  
Ginsenoside Compound K

Effects of cadmium on hepatic gluconeogenesis in vivo and in vitro

1984 ◽  
Vol 12 (5) ◽  
pp. 794-795 ◽  
Author(s):  
IAN N. ROBINSON ◽  
KEITH SNELL
Keyword(s):  
Hepatic Gluconeogenesis

scholarly journals Membrane-Bound Protein Kinase A Inhibits Smooth Muscle Cell Proliferation In Vitro and In Vivo by Amplifying cAMP–Protein Kinase A Signals

2001 ◽  
Vol 88 (3) ◽  
pp. 319-324 ◽  
Author(s):  
Ciro Indolfi ◽  
Eugenio Stabile ◽  
Carmela Coppola ◽  
Adriana Gallo ◽  
Cinzia Perrino ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cell ◽  
Protein Kinase A ◽  
Membrane Bound ◽  
Proliferation In Vitro ◽  
Kinase A

scholarly journals Evidence that the stimulation of lipogenesis in the mammary glands of starved lactating rats re-fed with a chow diet is dependent on continued hepatic gluconeogenesis during the absorptive period. Effects of a gluconeogenic inhibitory, mercaptopicolinic acid, in vivo

1985 ◽  
Vol 228 (3) ◽  
pp. 727-733 ◽  
Author(s):  
D H Williamson ◽  
V Ilic ◽  
R G Jones
Keyword(s):  
Mammary Gland ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Mammary Glands ◽  
Hepatic Glycogen ◽  
Chow Diet ◽  
Hepatic Gluconeogenesis ◽  
Rapid Stimulation ◽  
Stimulation Of

The rapid stimulation of lipogenesis in mammary gland that occurs on re-feeding starved lactating rats with a chow diet was decreased (60%) by injection of mercaptopicolinic acid, an inhibitor of hepatic gluconeogenesis at the phosphoenolpyruvate carboxykinase step. Mercaptopicolinate had no effect on lipogenesis in mammary glands of fed lactating rats. The inhibition of lipogenesis persisted in vitro when acini from mammary glands of re-fed rats treated with mercaptopicolinate were incubated with [1-14C]glucose. Mercaptopicolinate added in vitro had no significant effect on lipogenesis in acini from starved-re-fed lactating rats. Mercaptopicolinate prevented the deposition of glycogen and increased the rate of lipogenesis in livers of starved-re-fed lactating rats, whereas it had no significant effect on livers of fed lactating rats. Administration of intraperitoneal glucose restored the rate of mammary-gland lipogenesis in re-fed rats treated with mercaptopicolinate to the values for re-fed rats. Hepatic glycogen deposition was also restored, and the rate of hepatic lipogenesis was stimulated 5-fold. It is concluded that stimulation of mammary-gland lipogenesis on re-feeding with a chow diet after a period of starvation is in part dependent on continued hepatic gluconeogenesis during the absorptive period. Possible sources of the glucose precursors are discussed.

Effect of Compound K, a Metabolite of Ginseng Saponin, Combined with γ-Ray Radiation in Human Lung Cancer Cells in Vitro and in Vivo

2009 ◽  
Vol 57 (13) ◽  
pp. 5777-5782 ◽  
Author(s):  
Sungwook Chae ◽  
Kyoung Ah Kang ◽  
Weon Young Chang ◽  
Min Jung Kim ◽  
Su Jae Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Compound K ◽  
Ginseng Saponin ◽  
Human Lung Cancer Cells ◽  
Γ Ray

scholarly journals The Wnt signaling pathway effector TCF7L2 is upregulated by insulin and represses hepatic gluconeogenesis

2012 ◽  
Vol 303 (9) ◽  
pp. E1166-E1176 ◽  
Author(s):  
Wilfred Ip ◽  
Weijuan Shao ◽  
Yu-ting Alex Chiang ◽  
Tianru Jin
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Wnt Signaling ◽  
Wnt Signaling Pathway ◽  
Glucose Production ◽  
Hepatic Gluconeogenesis

Certain single nucleotide polymorphisms (SNPs) in transcription factor 7-like 2 (TCF7L2) are strongly associated with the risk of type 2 diabetes. TCF7L2 and β-catenin (β-cat) form the bipartite transcription factor cat/TCF in stimulating Wnt target gene expression. cat/TCF may also mediate the effect of other signaling cascades, including that of cAMP and insulin in cell-type specific manners. As carriers of TCF7L2 type 2 diabetes risk SNPs demonstrated increased hepatic glucose production, we aimed to determine whether TCF7L2 expression is regulated by nutrient availability and whether TCF7L2 and Wnt regulate hepatic gluconeogenesis. We examined hepatic Wnt activity in the TOPGAL transgenic mouse, assessed hepatic TCF7L2 expression in mice upon feeding, determined the effect of insulin on TCF7L2 expression and β-cat Ser675 phosphorylation, and investigated the effect of Wnt activation and TCF7L2 knockdown on gluconeogenic gene expression and glucose production in hepatocytes. Wnt activity was observed in pericentral hepatocytes in the TOPGAL mouse, whereas TCF7L2 expression was detected in human and mouse hepatocytes. Insulin and feeding stimulated hepatic TCF7L2 expression in vitro and in vivo, respectively. In addition, insulin activated β-cat Ser675 phosphorylation. Wnt activation by intraperitoneal lithium injection repressed hepatic gluconeogenic gene expression in vivo, whereas lithium or Wnt-3a reduced gluconeogenic gene expression and glucose production in hepatic cells in vitro. Small interfering RNA-mediated TCF7L2 knockdown increased glucose production and gluconeogenic gene expression in cultured hepatocytes. These observations suggest that Wnt signaling and TCF7L2 are negative regulators of hepatic gluconeogenesis, and TCF7L2 is among the downstream effectors of insulin in hepatocytes.

scholarly journals Transcriptional repression of the gluconeogenic gene PEPCK by the orphan nuclear receptor SHP through inhibitory interaction with C/EBPα

2007 ◽  
Vol 402 (3) ◽  
pp. 567-574 ◽  
Author(s):  
Min Jung Park ◽  
Hee Jeong Kong ◽  
Hye Young Kim ◽  
Hyeong Hoe Kim ◽  
Joon Hong Kim ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Transcriptional Repression ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Regulatory Element ◽  
Direct Interaction ◽  
Orphan Nuclear Receptor ◽  
Hepatic Gluconeogenesis ◽  
Inhibitory Interaction

SHP (short heterodimer partner) is an orphan nuclear receptor that plays an important role in regulating glucose and lipid metabolism. A variety of transcription factors are known to regulate transcription of the PEPCK (phosphoenolpyruvate carboxykinase) gene, which encodes a rate-determining enzyme in hepatic gluconeogenesis. Previous reports identified glucocorticoid receptor and Foxo1 as novel downstream targets regulating SHP inhibition [Borgius, Steffensen, Gustafsson and Treuter (2002) J. Biol. Chem. 277, 49761–49796; Yamagata, Daitoku, Shimamoto, Matsuzaki, Hirota, Ishida and Fukamizu (2004) J. Biol. Chem. 279, 23158–23165]. In the present paper, we show a new molecular mechanism of SHP-mediated inhibition of PEPCK transcription. We also show that the CRE1 (cAMP regulatory element 1; −99 to −76 bp relative to the transcription start site) of the PEPCK promoter is also required for the inhibitory regulation by SHP. SHP repressed C/EBPα (CCAAT/enhancer-binding protein α)-driven transcription of PEPCK through direct interaction with C/EBPα protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPα and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription. Taken together, these results suggest that SHP might regulate a level of hepatic gluconeogenesis driven by C/EBPα activation.

scholarly journals Full-length cardiac Na+/Ca2+ exchanger 1 protein is not phosphorylated by protein kinase A

2011 ◽  
Vol 300 (5) ◽  
pp. C989-C997 ◽  
Author(s):  
Pimthanya Wanichawan ◽  
William E. Louch ◽  
Kristin H. Hortemo ◽  
Bjørg Austbø ◽  
Per Kristian Lunde ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Caspase 3 ◽  
Fluorescent Protein ◽  
Mutational Analysis ◽  
Phosphorylation Site ◽  
Full Length ◽  
Kinase A

The cardiac Na+/Ca2+ exchanger 1 (NCX1) is an important regulator of intracellular Ca2+ homeostasis and cardiac function. Several studies have indicated that NCX1 is phosphorylated by the cAMP-dependent protein kinase A (PKA) in vitro, which increases its activity. However, this finding is controversial and no phosphorylation site has so far been identified. Using bioinformatic analysis and peptide arrays, we screened NCX1 for putative PKA phosphorylation sites. Although several NCX1 synthetic peptides were phosphorylated by PKA in vitro, only one PKA site (threonine 731) was identified after mutational analysis. To further examine whether NCX1 protein could be PKA phosphorylated, wild-type and alanine-substituted NCX1-green fluorescent protein (GFP)-fusion proteins expressed in human embryonic kidney (HEK)293 cells were generated. No phosphorylation of full-length or calpain- or caspase-3 digested NCX1-GFP was observed with purified PKA-C and [γ-32P]ATP. Immunoblotting experiments with anti-PKA substrate and phosphothreonine-specific antibodies were further performed to investigate phosphorylation of endogenous NCX1. Phospho-NCX1 levels were also not increased after forskolin or isoproterenol treatment in vivo, in isolated neonatal cardiomyocytes, or in total heart homogenate. These data indicate that the novel in vitro PKA phosphorylation site is inaccessible in full-length as well as in calpain- or caspase-3 digested NCX1 protein, suggesting that NCX1 is not a direct target for PKA phosphorylation.

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