title: Leptin relieves intestinal ischemia/reperfusion injury by promoting ERK1/2 phosphorylation and the NO signaling pathway.
abstract: BACKGROUND
  Recently, research has indicated that leptin plays a protective role in traumatic brain and liver injury. We studied the protective effect of leptin on intestinal I/R injury and examined its mechanism by using mice intestinal I/R model and murine peritoneal macrophage hypoxia/reoxygenation (H/R) injury model.
  
  
  METHODS
  Leptin was intraperitoneally administrated at 45 minutes after ischemia, then reperfusion for two hours. Cells were treated with different concentrations of leptin at three hours after hypoxia, then reoxygenation for six hours. Mice intestines were harvested for histopathologic properties. The malondialdehyde, nitric oxide (NO), interleukin-6, and total antioxidative capacity were detected according to respective assay kit. Phosphorylated extracellular regulated kinase1/2 (p-ERK1/2) and phosphorylated cytosolic phospholipase A(2) (p-cPLA2) were determined by Western blot assay.
  
  
  RESULTS
  Here, we show that leptin reduced intestinal histologic alterations, malondialdehyde and interleukin-6 levels but increased the endogenous leptin expression and NO production in the intestines. Leptin also increased the NO and total antioxidative capacity levels in cells. We further demonstrated that leptin markedly activated ERK1/2 in the intestines and activated ERK1/2 and cPLA2 in the cells. Moreover, the protective effect of leptin against intestinal I/R injury and elevated NO production was attenuated by blocking the ERK1/2 pathway.
  
  
  CONCLUSIONS
  These data demonstrate that leptin ameliorated intestinal I/R and peritoneal macrophage H/R injury by enhancing ERK1/2 phosphorylation and promoting the NO production signaling pathway.
authors.affiliation: Research Laboratory of Biochemistry, Basic Medical Institute, General Hospital of PLA, Beijing, People's Republic of China.
authors.forename: Zi-Hui
authors.initials: ZH
authors.lastname: Deng
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Yan
authors.forename: Lu-Huan
authors.initials: LH
authors.lastname: Wang
authors.forename: Jin-Ying
authors.initials: JY
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000032:analysis; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects*; D020738:Leptin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D054467:Phospholipases A2 / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000975:Antioxidants; D015850:Interleukin-6; D020738:Leptin; D009569:Nitric Oxide; D008315:Malondialdehyde; D054467:Phospholipases A2