Premium
Cerebella of young copper deficient rats have increased AMPK phosphorylation but decreased fructose 2,6 bisphosphate levels
Author(s) -
Gybina Anna A,
Prohaska Joseph R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a723-a
Subject(s) - ampk , phosphorylation , medicine , endocrinology , amp activated protein kinase , protein kinase a , chemistry , acetyl coa carboxylase , pyruvate carboxylase , metabolism , biology , biochemistry , enzyme
Cerebellar developmental delays following dietary copper (Cu) deficiency may be due to altered energy metabolism. To test Cu's effect, energy status was evaluated in fast frozen cerebella from Cu adequate (Cu+) and deficient (Cu−) 24 day old rat pups, born to dams placed on treatments at embryonic day 7 and continued through lactation. Selected metabolites were assessed, as was the phosphorylation state of AMP activated protein kinase (AMPK), a cellular energy sensor. Compared to controls, Cu‐ cerebellar [lactate] was three fold higher, but [ATP] and [AMP] were unaltered. However, immunoblots revealed higher levels of phospho‐AMPK (P<0.05) in Cu‐ cerebella, and were verified by increased phosphorylation of acetyl‐CoA carboxylase, an AMPK target. Surprisingly, fructose 2,6 bisphosphate (F2,6BP), which in astrocytes increases with AMPK activation as the product of AMPK target phosphofructokinase 2, was reduced by 50% in Cu‐ cerebella (P<0.05). Our conclusions are: Cu deficiency alters cerebellar energy metabolism, as shown by increased AMPK phosphorylation, which may sustain [ATP] and [AMP] at control levels; AMPK activation in Cu‐ cerebella did not result in higher [F2,6BP], suggesting differential regulation of AMPK in different cerebellar cell types. Studies in other Cu‐ rat tissues are underway to confirm these observations. Supported in part by NIH grant HD 39708.