Abstract:
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.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Pallottini V,Martini C,Cavallini G,Bergamini E,Mustard KJ,Hardie DG,Trentalance Adoi
10.1016/j.mad.2007.10.001subject
Has Abstractpub_date
2007-11-01 00:00:00pages
688-95issue
11-12eissn
0047-6374issn
1872-6216pii
S0047-6374(07)00162-5journal_volume
128pub_type
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