XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
43.
RegulaTION of EXPrESSION of PLaKOGLOBIN, a KEY DESMOSOMal
CONSTITUENT, BY arYL HYDrOCarBON rECEPTOr aND CaMP
SIGNaLING
Jiřina Procházková 1,2 , Lenka Umannová 1,2 , Alois Kozubík 1 ,
Miroslav Machala 2 and Jan Vondráček 1,2
1
Department of Cytokinetics, Insitute of Biophysics AS CR, Brno, 2 Department of
toxicology, pharmacology and immunology, Veterinary Research Insitute, Brno
Aryl hydrocarbon receptor (AhR) has been originally described as a transcription factor
mediating the toxic effects of dioxin-like compounds, but its signaling can be triggered
also by endogenous agents, such as second messenger cyclic adenosine monophosphate
(cAMP). Using an in vitro model of liver progenitor cells, participating both in liver
regeneration and in hepatocarcinogenesis, we first investigated the potency of cAMP
and another protein kinase A activator, forskolin, to activate AhR signaling pathway,
as analyzed at the level of: i) AhR nuclear uptake; ii) AhR protein degradation; and iii)
induction of model target gene Cyp1a1. We further analyzed the potency of cAMP and
forskolin, alone or in combination with dioxin to modulate expression of Jup gene encoding
plakoglobin protein, which plays a key role in establishment of intercellular junctions.
Using WB-F344 cells, we found that cAMP and forskolin may transiently activate AhR
signaling. As both compounds were able to modulate TCDD-induced changes in Cyp1a1
and Jup expression, our results support the existence of a possible link between cAMPactivated
signaling and AhR in regulation of both structural and signaling functions of
desmosomal and adherent junctions.
Acknowledgement: This work was funded by the Czech Science Foundation, grants No.
524/09/1337 and 305/09/1526].
XXII. Biochemistry Congress, Martin
161