The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Ethanol-induced modulation of hepatocellular extracellular signal-regulated kinase-1/2 activity via 4-hydroxynonenal.

Modulation of the extracellular signal-regulated kinases (ERK-1/2), a signaling pathway directly associated with cell proliferation, survival, and homeostasis, has been implicated in several pathologies, including alcoholic liver disease. However, the underlying mechanism of ethanol-induced ERK-1/2 modulation remains unknown. This investigation explored the effects of ethanol-associated oxidative stress on constitutive hepatic ERK-1/2 activity and assessed the contribution of the lipid peroxidation product 4-hydroxynonenal (4-HNE) to the observations made in vivo. Constitutive ERK-1/2 phosphorylation was suppressed in hepatocytes isolated from rats chronically consuming ethanol for 45 days. This observation was associated with an increase in 4-HNE-ERK monomer adduct concentration and a hepatic cellular and lobular redistribution of ERK-1/2 that correlated with 4-HNE-protein adduct accumulation. Chronic ethanol consumption was also associated with a decrease in hepatocyte nuclear ELK-1 phosphorylation, independent of changes in total nuclear ELK-1 protein. Primary hepatocytes treated with concentrations of 4-HNE consistent with those occurring during oxidative stress displayed a concentration-dependent decrease in constitutive ERK-1/2 phosphorylation, activity, and nuclear localization that negatively correlated with 4-HNE-ERK-1/2 monomer adduct accumulation. These data paralleled the decreased phosphorylation of the downstream kinase ELK-1. Molar ratios of purified ERK-2 to 4-HNE consistent with pathologic ratios found in vivo resulted in protein monomer-adduct formation across a range of concentrations. Collectively, these data demonstrate a novel association between ethanol-induced lipid peroxidation and the inhibition of constitutive ERK-1/2, and suggest an inhibitory mechanism mediated by the lipid peroxidation product 4-hydroxynonenal.[1]

References

 
WikiGenes - Universities