title: Knock-out of β-glucosidase 2 has no influence on dextran sulfate sodium-induced colitis.
abstract: OBJECTIVE
  The non-lysosomal glucosylceramidase, β-glucosidase (Gba2), hydrolyzes glucosylceramide to glucose and ceramide (Cer). Cer is a potent second-messenger lipid that plays an important role in signaling cascades involved in apoptosis. The aim of this study was to investigate whether Gba2 knock-out (Gba2(-/-)) affects the extent of dextran sulfate sodium (DSS)-induced colitis in mice.
  
  
  METHODS
  Acute colitis was induced in wild-type (WT) and Gba2(-/-) mice by administration of 2% DSS in drinking water. After 7 days, mice underwent colonoscopy and were sacrificed.
  
  
  RESULTS
  Both DSS-treated WT (n = 10) and Gba2(-/-) (n = 12) mice showed elevated histological and endoscopic scores compared to respective H(2)O controls (n = 9 each). However, no significant differences between the DSS groups were detected. Flow cytometric analysis of propidium iodide staining, cleavage of caspases-3 and -8, indicative for apoptosis, as well as Cer levels were not altered in DSS-treated WT or Gba2(-/-) mice. Gba2(-/-) resulted in slightly decreased expression of glucocerebrosidase (Gba1) as well as in upregulation of proteins being involved in cellular regeneration, such as STAT3 (signal transducer and activator of transcription), JNK and iNOS, upon DSS treatment.
  
  
  CONCLUSIONS
  We demonstrate that Gba2(-/-) does not affect the extent of DSS-induced inflammation in mice, however, it might be involved in tissue regeneration in response to toxic agents.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.forename: Katharina
authors.initials: K
authors.lastname: Leucht
authors.forename: Isabelle
authors.initials: I
authors.lastname: Frey-Wagner
authors.forename: Jonas
authors.initials: J
authors.lastname: Zeitz
authors.forename: Martin
authors.initials: M
authors.lastname: Hausmann
authors.forename: Anne
authors.initials: A
authors.lastname: Fischbeck
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Silvia
authors.initials: S
authors.lastname: Kellermeier
authors.forename: Theresa
authors.initials: T
authors.lastname: Pesch
authors.forename: Joba
authors.initials: J
authors.lastname: Arikkat
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Yildiz
authors.initials: Y
authors.lastname: Yildiz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D003106:Colon / Q000201:enzymology* / Q000473:pathology*; D003113:Colonoscopy; D016264:Dextran Sulfate / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D005962:Glucosylceramidase / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation; D001617:beta-Glucosidase / Q000235:genetics*
chemical_list: D002518:Ceramides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D001617:beta-Glucosidase; C517538:beta-glucosidase 2, mouse; D005962:Glucosylceramidase; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8