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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Age-related HMG-CoA reductase deregulation depends on ROS-induced p38 activation.

BACKGROUND: It seems to be clear that hepatic age-related HMG-CoA reductase total activation is connected to a rise of reactive oxygen species (ROS). However, the mechanism by which ROS achieve this effect is unknown. Thus, in this work, we have performed a study of HMG-CoAR by analyzing the enzymes involved in its short-term regulation, namely, AMP-activated kinase (AMPK) and protein phosphatase 2A (PP2A). METHODS AND MATERIALS: In the liver of aged rats and in H(2)O(2)-stimulated HepG2 cells the ROS content, the HMG-CoA reductase activation state, its regulatory enzymes and the p38 downstream pathway involved in reductase deregulation, have been studied. RESULTS AND CONCLUSIONS: Our data show that the hepatic HMG-CoAR is completely dephosphorylated in the liver of old rat being the PP2A increased association with HMG-CoAR the main responsible. On the other hand, the age-related greater association between PP2A and HMG-CoAR results to be due to an increase in ROS that is present during aging and has already been demonstrated to influence HMG-CoAR activation state. Moreover, H(2)O(2)-stimulated HepG2 cell line shows that the ROS effect on the HMG-CoAR dephosphorylation is mediated by the activation of p38/MAPK pathway.[1]

References

  1. Age-related HMG-CoA reductase deregulation depends on ROS-induced p38 activation. Pallottini, V., Martini, C., Cavallini, G., Bergamini, E., Mustard, K.J., Hardie, D.G., Trentalance, A. Mech. Ageing Dev. (2007) [Pubmed]
 
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