Cyclic AMP increases rat inhibitor of apoptosis protein (RIAP1) mRNA in renal mesangial cells.
BACKGROUND
The cyclic adenosine 3',5'-monophosphate (cAMP) pathway plays a central role in the regulation of cell proliferation, differentiation and apoptosis. Cyclic AMP has been identified as a bifunctional regulator of apoptosis. The inhibitor of apoptosis proteins (IAP) regulates apoptosis by directly inhibiting distinct caspases.


METHODS
Expression levels of rat IAP (RIAP)-1 were investigated by RNase protection assay in rat mesangial cells after stimulation with diverse agents that modulate cellular levels of cAMP.


RESULTS
Rat mesangial cells up-regulated RIAP1 mRNA levels after cAMP stimulation. Membrane-permeable cAMP analogs, as well as cAMP production in response to the beta-adrenergic receptor agonist salbutamol caused a large increase in RIAP1 mRNA level, which could be inhibited by the protein kinase A inhibitors H89 and Rp-cAMPS, or by the nuclear factor-kappaB (NF-kappaB) inhibitor BAY117085. Inhibition of phosphodiesterase type IV by denbufyllin or rolipram potentiated the cAMP-mediated increase in RIAP1 mRNA. In contrast, the cyclic guanosine 3',5'-monophosphate (cGMP) analog Bt2cGMP did not affect the RIAP1 mRNA level.


CONCLUSIONS
These data establish, to our knowledge for the first time, that RIAP1 mRNA levels are regulated by the cAMP-signaling pathway and suggest potential new avenues of therapy to modulate apoptosis.
Manderscheid
Markus
M
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Pereda-Fernández
Carmen
C
Pfeilschifter
Josef
J
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D013873:Thionucleotides; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP