Involvement of mTOR in globular adiponectin-induced generation of reactive oxygen species.
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.
Fujimoto
Akie
A
Department of Preventive Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Akifusa
Sumio
S
Kamio
Noriaki
N
Hirofuji
Takao
T
Nonaka
Kazuaki
K
Yamashita
Yoshihisa
Y
D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases; D013876:Thiophenes / Q000494:pharmacology; D000077191:Wortmannin
D052242:Adiponectin; D000620:Aminoimidazole Carboxamide; D000730:Androstadienes; D001713:Biphenyl Compounds; D003847:Deoxyglucose; D047908:Intracellular Signaling Peptides and Proteins; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011753:Pyrones; D017382:Reactive Oxygen Species; D012265:Ribonucleotides; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D013876:Thiophenes; D000077191:Wortmannin; C546843:mTOR protein, mouse; C031143:AICA ribonucleotide; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile