PMID- 18160324 OWN - NLM STAT- MEDLINE DCOM- 20080429 LR - 20211203 IS - 1098-8823 (Print) IS - 1098-8823 (Linking) VI - 85 IP - 1-2 DP - 2008 Feb TI - PGF2alpha-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN. PG - 49-57 AB - Prostaglandin F2alpha (PGF2alpha) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2alpha-induced VSMC hypertrophy we examined the ability of the PGF2alpha analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6k), glycogen synthase kinase-3beta (GSK-3beta), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3beta, PTEN and ERK1/2 but not JNK phosphorylation. Whereas inhibition of phosphatidylinositol 3-kinase (PI3K) by LY-294002 blocked fluprostenol-induced changes in total protein content, pre-treatment with rapamycin or with the MEK1/2 inhibitor U0126 did not. Taken together, these findings suggest that fluprostenol-induced changes in A7r5 hypertrophy involve mTOR translocation and occur through PI3K-dependent mechanisms. FAU - Rice, K M AU - Rice KM AD - Department of Biological Sciences, Marshall University, Huntington, WV 25755-1090, USA. rice@marshall.edu FAU - Uddemarri, S AU - Uddemarri S FAU - Desai, D H AU - Desai DH FAU - Morrison, R G AU - Morrison RG FAU - Harris, R AU - Harris R FAU - Wright, G L AU - Wright GL FAU - Blough, E R AU - Blough ER LA - eng GR - R15 AG027103/AG/NIA NIH HHS/United States GR - P20 RR016477/RR/NCRR NIH HHS/United States GR - R15 AG027103-01/AG/NIA NIH HHS/United States GR - RR16477/RR/NCRR NIH HHS/United States GR - AG-20370/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20071117 PL - United States TA - Prostaglandins Other Lipid Mediat JT - Prostaglandins & other lipid mediators JID - 9808648 RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Prostaglandins F, Synthetic) RN - 0 (Reactive Oxygen Species) RN - 358S7VUE5N (fluprostenol) RN - B7IN85G1HY (Dinoprost) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (Pten protein, mouse) SB - IM MH - Animals MH - Blotting, Western MH - Cell Line MH - Dinoprost/agonists/*physiology MH - Fluorescent Antibody Technique MH - MAP Kinase Signaling System MH - Microscopy, Fluorescence MH - Muscle, Smooth, Vascular/*pathology MH - PTEN Phosphohydrolase/*metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Prostaglandins F, Synthetic/pharmacology MH - Protein Kinases/drug effects/*metabolism MH - Rats MH - Reactive Oxygen Species/*metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors/*metabolism MH - TOR Serine-Threonine Kinases PMC - PMC2277510 MID - NIHMS39450 EDAT- 2007/12/28 09:00 MHDA- 2008/04/30 09:00 PMCR- 2009/02/01 CRDT- 2007/12/28 09:00 PHST- 2006/05/08 00:00 [received] PHST- 2007/07/12 00:00 [revised] PHST- 2007/10/26 00:00 [accepted] PHST- 2007/12/28 09:00 [pubmed] PHST- 2008/04/30 09:00 [medline] PHST- 2007/12/28 09:00 [entrez] PHST- 2009/02/01 00:00 [pmc-release] AID - S1098-8823(07)00122-0 [pii] AID - 10.1016/j.prostaglandins.2007.10.009 [doi] PST - ppublish SO - Prostaglandins Other Lipid Mediat. 2008 Feb;85(1-2):49-57. doi: 10.1016/j.prostaglandins.2007.10.009. Epub 2007 Nov 17.