title: Prostaglandin E2 negatively regulates AMP-activated protein kinase via protein kinase A signaling pathway.
abstract: We investigated possible involvement of prostaglandin (PG) E2 in regulation of AMP-activated protein kinase (AMPK). When osteoblastic MG63 cells were cultured in serum-deprived media, Thr-172 phosphorylation of AMPK alpha-subunit was markedly increased. Treatment of the cells with PGE2 significantly reduced the phosphorylation. Ser-79 phosphorylation of acetyl-CoA carboxylase, a direct target for AMPK, was also reduced by PGE2. On the other hand, PGE2 reciprocally increased Ser-485 phosphorylation of the alpha-subunit that could be associated with inhibition of AMPK activity. These effects of PGE2 were mimicked by PGE2 receptor EP2 and EP4 agonists and forskolin, but not by EP1 and EP3 agonists, and the effects were suppressed by an adenylate cyclase inhibitor SQ22536 and a protein kinase A inhibitor H89. Additionally, the PGE2 effects were duplicated in primary calvarial osteoblasts. Together, the present study demonstrates that PGE2 negatively regulates AMPK activity via activation of protein kinase A signaling pathway.
authors.affiliation: Department of Endocrinology, Research Institute of Environmental Medicine (RIEM), Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Funahashi
authors.forename: Xia
authors.initials: X
authors.lastname: Cao
authors.forename: Masako
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kozaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Fukushi
authors.initials: F
authors.lastname: Kambe
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000201:enzymology; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D015232:Dinoprostone