Caffeine-induced telencephalic vesicle evagination in early post-implantation mouse embryos involves cAMP-dependent protein kinase (PKA) inhibition.
Other studies have shown that caffeine accelerates telencephalic vesicle evagination in early post-implantation mouse embryos. The present study examines the effect of caffeine on gene modulation in post-implantation mouse embryos. Using mRNA differential display, we observed that caffeine increased gene expression of the regulatory subunit (RI alpha) of cAMP-dependent protein kinase (PKA). RT--PCR analysis confirmed an increase in expression of this gene in caffeine-exposed embryos when compared with saline-treated controls. Using a fluorescent substrate of PKA, we found that PKA activity in the presence of cAMP was lower in caffeine-treated embryos than in controls. Treatment with H89 and PKI(12-24)amide, two inhibitors of PKA activity, mimicked the effects of caffeine on telencephalic vesicle formation. Together these data suggest that in early post-implantation mouse embryos caffeine modulates gene expression of the RI alpha subunit of PKA and that caffeine-induced inhibition of PKA activity plays a role in early telencephalic evagination.
INSERM E 9935, Hôpital Robert-Debré, Paris, France.
N
N
Sahir
C
C
Mas
F
F
Bourgeois
M
M
Simonneau
P
P
Evrard
P
P
Gressens
D000818:Animals; D001483:Base Sequence; D002110:Caffeine / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; C015482:protein kinase modulator; D002110:Caffeine; D017868:Cyclic AMP-Dependent Protein Kinases