Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element binding protein 1 activity by way of the calcium/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mechanistic target of rapamycin-p70 ribosomal S6 kinase signaling

2016 ◽  
Vol 47 (7) ◽  
pp. 683-701 ◽  
Author(s):  
Shaojie Wang ◽  
Xiaojie Li ◽  
Hongli Guo ◽  
Zihang Yuan ◽  
Tao Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Hepatic Steatosis ◽  
Regulatory Element ◽  
S6 Kinase ◽  
Mechanistic Target Of Rapamycin ◽  
Calcium Calmodulin Dependent ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Ribosomal S6 Kinase ◽  
Amp Activated Protein Kinase

scholarly journals Regulation of hepatic lipin-1 by ethanol: Role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice

Hepatology ◽  
2011 ◽  
Vol 55 (2) ◽  
pp. 437-446 ◽  
Author(s):  
Ming Hu ◽  
Fengming Wang ◽  
Xin Li ◽  
Christopher Q. Rogers ◽  
Xiaomei Liang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Lipin 1 ◽  
Sterol Regulatory Element ◽  
Amp Activated Protein Kinase

scholarly journals Analysis of the role of protein kinase B (cAKT) in insulin-dependent induction of glucokinase and sterol regulatory element-binding protein 1 (SREBP1) mRNAs in hepatocytes

2003 ◽  
Vol 376 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Pascale G. RIBAUX ◽  
Patrick B. IYNEDJIAN
Keyword(s):  
Protein Kinase ◽  
Protein Kinase B ◽  
Binding Protein ◽  
Regulatory Element ◽  
Necessary Condition ◽  
Insulin Effect ◽  
Element Binding Protein ◽  
Insulin Dependent ◽  
Sterol Regulatory Element ◽  
Stimulation Of

Previous work showed that acute stimulation of a conditionally active protein kinase B (PKB or cAKT) was sufficient to elicit insulin-like induction of GCK (glucokinase) and SREBP1 (sterol regulatory element-binding protein 1) in hepatocytes [Iynedjian, Roth, Fleischmann and Gjinovci (2000) Biochem. J. 351, 621–627; Fleischmann and Iynedjian (2000) Biochem. J. 349, 13–17]. The objective of the present study was to determine whether activation of PKB during insulin stimulation of hepatocytes was a necessary condition for the induction of the two genes. Activation of PKB by insulin was inhibited by pretreatment of the hepatocytes with C2 ceramide. This resulted in the inhibition of insulin-dependent increases in GCK and SREBP1 mRNAs. A triple mutant of PKB failed to interfere with insulin activation of PKB in hepatocytes even at high overexpression levels achieved after adenovirus transduction. A PKB–CaaX fusion protein, which can act as a dominant-negative inhibitor of PKB activation in other cells, was shown to be constitutively activated in hepatocytes and to trigger insulin-like induction of GCK and SREBP1. In addition, constitutive PKB–CaaX activity caused refractoriness of the hepatocytes to insulin signalling at an upstream step resulting in the inhibition of both extracellular-signal-regulated kinase 1/2 and endogenous PKB activation. The stimulation of gene expression by constitutively active PKB–CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1.

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