title: Guanylyl cyclase-G modulates jejunal apoptosis and inflammation in mice with intestinal ischemia and reperfusion.
abstract: BACKGROUND
  Membrane bound guanylyl cyclase-G (mGC-G), a novel form of GC mediates ischemia and reperfusion (IR)-induced renal injury. We investigated the roles of mGC-G in intestinal IR-induced jejunal damage, inflammation, and apoptosis.
  
  
  METHODS
  Male C57BL/6 wild-type (WT) and mGC-G gene knockout (KO) mice were treated with a sham operation or 45 min of superior mesenteric arterial obstruction followed by 3, 6, 12, or 24 h of reperfusion.
  
  
  RESULTS
  Sham-operated KO mice had significantly lower plasma nitrate and nitrite (NOx) levels and jejunal villus height, crypt depth, and protein expression of phosphorylated-nuclear factor-kappa-B (NF-κB), phosphorylated-c-Jun N-terminal kinases (JNK) 2/3, phosphorylated-p38, and B-cell lymphoma-2 (Bcl-2). They had significantly greater jejunal interleukin-6 mRNA, cytochrome c protein, and apoptotic index compared with sham-operated WT mice. Intestinal IR significantly decreased plasma NOx in WT mice and increased plasma NOx in KO mice. The jejunal apoptotic index and caspase 3 activities were significantly increased, and nuclear phosphorylated-NF-κB and phosphorylated-p38 protein were significantly decreased in WT, but not KO mice with intestinal IR. After reperfusion, KO mice had an earlier decrease in jejunal cyclic GMP, and WT mice had an earlier increase in jejunal proliferation and a later increase in cytosol inhibitor of kappa-B-alpha. Intestinal IR induced greater increases in plasma and jejunal interleukin-6 protein in WT mice and a greater increase in jejunal interleukin-6 mRNA in KO mice.
  
  
  CONCLUSIONS
  mGC-G is involved in the maintenance of jejunal integrity and intestinal IR-induced inflammation and apoptosis. These results suggest that targeting cGMP pathway might be a potential strategy to alleviate IR-induced jejunal damages.
authors.affiliation: Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lo
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Ruey-Bing
authors.initials: RB
authors.lastname: Yang
authors.affiliation: Division of Pediatric Surgery, Changhua Christian Hospital, Changhau, Taiwan; Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000139:chemically induced / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050705:Receptors, Guanylate Cyclase-Coupled / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000139:chemically induced / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D009566:Nitrates; D009573:Nitrites; D019253:Proto-Oncogene Proteins c-bcl-2; D000072000:NF-KappaB Inhibitor alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D050705:Receptors, Guanylate Cyclase-Coupled; C514217:guanylyl cyclase-G, mouse