Elevated CREB activity in embryonic fibroblasts of gene-targeted histamine deficient mice.
OBJECTIVE
Histamine is a known inducer of cAMP-responsive element binding protein (CREB), which plays a key role in initiation of adipogenesis. Our present goal was to study how histamine deficiency impacts CREB signalling and adipogenesis.


METHODS
We used a histidine-decarboxylase gene-targeted (HDC KO) mice model lacking endogenous histamine. We measured CREB activity and expression by EMSA, Western blot and real-time RT-PCR, as well as cAMP levels by ELISA in primary embryonic fibroblasts derived from WT and HDC KO mice. The ability of these cells to form adipocytes was also tested in preliminary experiments.


RESULTS
We found that in the absence of the histamine, cells show higher constitutive CREB activity and greatly increased intracellular cAMP levels, as well as that in contrast to WT cells, HDC KO fibroblasts are more prone to differentiate into adipocytes.


CONCLUSIONS
These data suggest a newly recognised inhibitory role for histamine in CREB activity and draws attention to the potential role of histamine in adipocyte differentiation.
Hegyi
K
K
Research Group for Immunogenomics, Hungarian Academy of Sciences, Semmelweis University, 4 Nagyvarad ter Budapest, 1089 Budapest, Hungary.
Falus
A
A
Toth
S
S
D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000032:analysis; D006640:Histidine Decarboxylase / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D011970:Receptors, Histamine H2 / Q000032:analysis
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D006634:Histamine H1 Antagonists; D011970:Receptors, Histamine H2; D006632:Histamine; D000242:Cyclic AMP; D006640:Histidine Decarboxylase