title: Globular adiponectin attenuates LPS-induced reactive oxygen species production in HepG2 cells via FoxO3A and HO-1 signaling.
abstract: OBJECTIVE
  Adiponectin has been shown to possess potent anti-oxidative properties in various experimental conditions. However, its anti-oxidative effects and underlying mechanisms have not been reported in liver cells. Herein, we investigated the effects of globular adiponectin (gAcrp) on LPS-stimulated reactive oxygen species (ROS) production and its mechanisms underlying in human hepatic cells (HepG2).
  
  
  METHODS
  Intracellular ROS production was determined by fluorescence of 5-chloromethyl-2,7-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). NADPH oxidase-dependent ROS formation was determined by lucigenin-derived chemiluminescence. Messenger RNA expression level of target genes was determined by quantitative RT-PCR and protein expression was measured by Western blot analysis.
  
  
  RESULTS
  LPS-induced increase in ROS production was prevented by pretreatment with gAcrp in HepG2 cells. Furthermore, gAcrp treatment suppressed LPS-induced activation of NADPH oxidase and increase in mRNA and protein expression of Nox-4. We also found that adiponectin increased expression of FoxO3A and HO-1 and ablation of either of these genes partially restored suppression of LPS-induced ROS production and NADPH oxidase activation by gAcrp, indicating the vital role of FoxO3A and HO-1 signaling in the inhibition of ROS production and NADPH oxidase activation by gAcrp.
  
  
  CONCLUSIONS
  These results suggest that gAcrp prevents LPS-induced ROS production and NADPH oxidase activity in HepG2 cells via FoxO3A and HO-1 signaling-dependent mechanisms. The present study demonstrated a suppressive effect of adiponectin on ROS production in liver cells and presented a novel mechanism underlying suppression of ROS production by adiponectin.
authors: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors: Anup
authors: A
authors: Shrestha
authors: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. Electronic address: parkp@yu.ac.kr.
authors: Pil-Hoon
authors: PH
authors: Park
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Adiponectin; FoxO3A; HO-1; HepG2; NADPH oxidase