Rolipram, a Phosphodiesterase 4 Inhibitor, Stimulates Inducible cAMP Early Repressor Expression in Osteoblasts.
10.3349/ymj.2005.46.1.149
- Author:
Eun Sook CHO
1
;
Ja Heon YU
;
Mi Sun KIM
;
Mijung YIM
Author Information
1. College of Pharmacy, Sookmyung Women's University, Seoul, Korea. myim@sookmyung.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Osteoblast;
cyclic AMP;
PDE4 inhibitor;
ICER
- MeSH:
3', 5'-Cyclic-Nucleotide Phosphodiesterase/*antagonists & inhibitors;
Animals;
Animals, Outbred Strains;
Cyclic AMP-Dependent Protein Kinases/metabolism;
DNA-Binding Proteins/genetics/*metabolism;
Gene Expression/drug effects;
Mice;
Osteoblasts/*drug effects/metabolism;
Phosphodiesterase Inhibitors/*pharmacology;
Research Support, Non-U.S. Gov't;
Rolipram/*pharmacology;
Transcription Factors/genetics/*metabolism;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Yonsei Medical Journal
2005;46(1):149-154
- CountryRepublic of Korea
- Language:English
-
Abstract:
Phosphodiesterase (PDE) 4 inhibitors have been shown to induce the cAMP-mediated signaling pathway by inhibiting cAMP hydrolysis. This study investigated the effect of a PDE4 inhibitor on the expression of the inducible cAMP early repressor (ICER), which is an endogenous inhibitor of CRE- mediated transcription, in osteoblastic cells. RT-PCR analysis revealed that rolipram, a PDE4 inhibitor, stimulates the ICER mRNA in a dose dependent manner. The induction of ICER mRNA expression by rolipram was suppressed by the inhibitors of protein kinase A (PKA) and p38 MAPK, suggesting the involvement of PKA and p38 MAPK activation in ICER expression by rolipram. It was previously shown that rolipram induced the expression of TNF-related activation-induced cytokine (TRANCE, also known as RANKL, ODF, or OPGL) in osteoblasts. This paper provides evidences that a transcriptional repressor like ICER might modulate TRANCE mRNA expression by rolipram in osteoblasts.
