1. Knock-Out of beta-Glucosidase 2 Has No Influence on Dextran Sulfate Sodium-Induced Colitis
- Author
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Jonas Zeitz, Silvia Kellermeier, Michael Scharl, Anne Fischbeck, Isabelle Frey-Wagner, Michael Fried, Martin Hausmann, Yildiz Yildiz, Theresa Pesch, Joba M. Arikkat, Gerd Schmitz, Katharina Leucht, Gerhard Liebisch, Gerhard Rogler, University of Zurich, and Rogler, G
- Subjects
STAT3 Transcription Factor ,Ceramide ,Colon ,610 Medizin ,Nitric Oxide Synthase Type II ,Apoptosis ,610 Medicine & health ,Ceramides ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Downregulation and upregulation ,medicine ,Animals ,2715 Gastroenterology ,Propidium iodide ,Colitis ,STAT3 ,Acute colitis ,030304 developmental biology ,Mice, Knockout ,Caspase 8 ,0303 health sciences ,ddc:610 ,biology ,Caspase 3 ,beta-Glucosidase ,Dextran Sulfate ,030302 biochemistry & molecular biology ,JNK Mitogen-Activated Protein Kinases ,Gastroenterology ,Epithelial Cells ,Colonoscopy ,medicine.disease ,G1 Phase Cell Cycle Checkpoints ,Molecular biology ,Up-Regulation ,3. Good health ,carbohydrates (lipids) ,10219 Clinic for Gastroenterology and Hepatology ,chemistry ,Biochemistry ,10032 Clinic for Oncology and Hematology ,STAT protein ,biology.protein ,Glucosylceramidase ,Female - Abstract
Background/Aims: 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 H2O 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. Conclusion: 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.
- Published
- 2011