PMID- 19886750 OWN - NLM STAT- MEDLINE DCOM- 20100415 LR - 20211203 IS - 1029-2470 (Electronic) IS - 1029-2470 (Linking) VI - 44 IP - 2 DP - 2010 Feb TI - Involvement of mTOR in globular adiponectin-induced generation of reactive oxygen species. PG - 128-34 LID - 10.3109/10715760903348328 [doi] AB - Globular adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO) in the murine macrophage cell line RAW 264. This study investigated the role of the mammalian target of rapamycin (mTOR) in gAd-induced ROS and NO generation. gAd stimulation induced phosphorylation of mTOR, which peaked at 20 min and dissolved rapidly. Inhibition of phosphatidylinositol 3-kinase activity with wortmannin suppressed gAd-induced phosphorylation of Akt and mTOR. Administration of rapamycin partially reduced gAd-induced generation of intracellular and mitochondrial ROS, but not release of NO. To further confirm the role of mTOR in gAd stimulation, the effect of the activators of AMP-activated protein kinase (AMPK) on gAd-induced mTOR phosphorylation was examined. Pre-treatment with three kinds of AMPK activators, AICAR, 2-deoxy-D-glucose and A-769662, suppressed gAd-induced mTOR phosphorylation. Furthermore, these AMPK activators significantly reduced gAd-evoked intracellular and mitochondrial ROS generation and NO release. FAU - Fujimoto, Akie AU - Fujimoto A AD - Department of Preventive Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. FAU - Akifusa, Sumio AU - Akifusa S FAU - Kamio, Noriaki AU - Kamio N FAU - Hirofuji, Takao AU - Hirofuji T FAU - Nonaka, Kazuaki AU - Nonaka K FAU - Yamashita, Yoshihisa AU - Yamashita Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Free Radic Res JT - Free radical research JID - 9423872 RN - 0 (Adiponectin) RN - 0 (Androstadienes) RN - 0 (Biphenyl Compounds) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Pyrones) RN - 0 (Reactive Oxygen Species) RN - 0 (Ribonucleotides) RN - 0 (Thiophenes) RN - 31C4KY9ESH (Nitric Oxide) RN - 360-97-4 (Aminoimidazole Carboxamide) RN - 9G2MP84A8W (Deoxyglucose) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - F0X88YW0YK (AICA ribonucleotide) RN - P68477CD2C (4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile) RN - W36ZG6FT64 (Sirolimus) RN - XVA4O219QW (Wortmannin) SB - IM MH - Adiponectin/antagonists & inhibitors/*pharmacology MH - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology MH - Androstadienes/pharmacology MH - Animals MH - Biphenyl Compounds MH - Cells, Cultured MH - Deoxyglucose/pharmacology MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Macrophages/drug effects/metabolism MH - Mice MH - Nitric Oxide/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation/drug effects MH - Protein Serine-Threonine Kinases/*metabolism MH - Pyrones/pharmacology MH - Reactive Oxygen Species/*metabolism MH - Ribonucleotides/pharmacology MH - Sirolimus/pharmacology MH - Structure-Activity Relationship MH - TOR Serine-Threonine Kinases MH - Thiophenes/pharmacology MH - Wortmannin EDAT- 2009/11/06 06:00 MHDA- 2010/04/16 06:00 CRDT- 2009/11/06 06:00 PHST- 2009/11/06 06:00 [entrez] PHST- 2009/11/06 06:00 [pubmed] PHST- 2010/04/16 06:00 [medline] AID - 10.3109/10715760903348328 [pii] AID - 10.3109/10715760903348328 [doi] PST - ppublish SO - Free Radic Res. 2010 Feb;44(2):128-34. doi: 10.3109/10715760903348328.