Article

Effects of WY-14,643 on the phosphorylation and activation of AMP-dependent protein kinase.

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, 545 N. Barnhill Drive, Indianapolis, IN 46202, USA.
Archives of Biochemistry and Biophysics (impact factor: 2.93). 03/2009; 485(1):10-5. DOI:10.1016/j.abb.2009.02.006 pp.10-5
Source: PubMed

ABSTRACT AMP-dependent protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR) alpha facilitate fatty acid oxidation. We have shown that treatment of hepatoma cells with ethanol or feeding ethanol-containing diets to mice inhibited both PPARalpha and AMPK activity. Importantly, WY-14,643 reversed the development of fatty liver in alcohol-fed mice. Whether WY-14,643, a PPARalpha agonist, has any effects on AMPK is not known. The aim of this study was to investigate the effect of WY-14,643 on AMPK activity.
The effect of WY-14,643 on AMPK phosphorylation and activity were examined in rat hepatoma cells (H4IIEC3). The effect of WY-14,643 on upstream kinases of AMPK, PKC-zeta/LKB1, intracellular AMP:ATP ratio, oxidative stress, and AMPK gene expression were studied.
Treatment of the H4IIEC3 cells with WY-14,643 for 24h led to 60% increase in the phosphorylation of AMPK. The effect of WY-14,643 on AMPK phosphorylation is PKC-zeta/LKB1 independent. WY-14,643 did not alter the levels of intracellular AMP:ATP ratio and it did not increase the levels of reactive oxygen species at 24-h of treatment. WY-14,643-induced AMPK alpha subunit expression by 2- to 2.5-fold, but there was no change in AMPKalpha subunit protein at 24h. The effect of WY-14,643 on AMPK phosphorylation did not altered by the presence of an NADPH oxidase inhibitor.
WY-14,643 induced AMPKalpha subunit phosphorylation and the activity of the enzyme. This was associated with induction of AMPKalpha1 and alpha2 mRNA, but the mechanism for this activation is uncertain.

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  • Article: Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC.
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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

alcohol-fed mice
 
alpha2 mRNA
 
AMP-dependent protein kinase
 
AMPK activity
 
AMPK gene expression
 
AMPK phosphorylation
 
AMPKalpha subunit protein
 
AMPKalpha1
 
fatty acid oxidation
 
fatty liver
 
H4IIEC3 cells
 
hepatoma cells
 
mice inhibited
 
NADPH oxidase inhibitor
 
peroxisome proliferator-activated receptor
 
PPARalpha agonist
 
rat hepatoma cells
 
reactive oxygen species
 
WY-14,643 induced AMPKalpha subunit phosphorylation
 
WY-14,643-induced AMPK alpha subunit expression
 

Suthat Liangpunsakul