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| 1 | Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease显示文摘AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides. | John J Miklavcic Glen K Shoemaker Vera C Mazurak M Tom Clandinin Tasha DL Hart Kareena L Schnabl Gordon M Lees Bodil MK Larsen Oliver F Bathe Alan BR Thomson M Tom Clandinin | 2015 | World Journal of Gastroenterology2015，21，35： | 3 |
| 2 | Hyperlycemia exacerbates muscle protein catabolism in burn-injured patients 显示文摘 | Gore DC Chinkes DL Hart DW | 2002 | Crit Care Med2002，30，11： | 1 |
| 3 | Cervical orthoses : a study comparing their effectiveness in restricting cervical motion in normal subjects显示文摘 | Johnso RM Hart DL Simmons EF | 1977 | J Bone Joint Surg Am1977，59，3： | 1 |
| 4 | Cervical orthosis显示文摘 | Hart DL Simmons EF et ai | 1977 | J Bone Joint Surg (Am)1977，59，5： | 1 |
| 5 | Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients显示文摘 | Gore DC Chinkes DL Hart DW | 2002 | Crit Care Med2002，30，11： | 1 |
| 6 | Cervical orthosis:a study comparing their effectiveness in restricting cervical motion in normal subjects显示文摘 | Johnson RM Hart DL Simmons EF | 1977 | J Bone Joint Surg Am1977，59，3： | 1 |
| 7 | Tumor initiating cancer stem cells from human breast cancer cell lines 显示文摘 | Hart JS Crowe DL | 2009 | Int J Oncol2009，34，5： | 1 |
| 8 | A Double blind, randomized, placebo controlled, parallel study to determine the efficacy of opiramate in the prophylactic treatment of nigraine显示文摘 | Potter DL Hart DE Calder CS | 2000 | Neurology2000，54，3： | 1 |
| 9 | A double-blind, randomized, placebo controlled parallel study to determine the efficacy of topiramate in the prophylactic tlreatment of migraine显示文摘 | Potter DL Hart DE Calder CS | 2000 | Neurology2000，54，3： | 1 |
| 10 | Hyperglycemia exacerbatesmuscle protein catabolismin burn-injured patients显示文摘 | Chinkes DL Hart DW | 2002 | Crit Care Med2002，30，11： | 1 |
| 11 | Cenlralization phenomenon as a prognostic factor for chronic low back pain and disability显示文摘 | Wemeke M Hart DL | 2001 | Spine (Phila Pa 1976)2001，26，7： | 1 |
| 12 | Increased tissue oxygen extraction and acidosis with progressive severity of sepsis显示文摘 | Chinkes DL Gore DC | 2003 | J of Surg Res2003，112，1： | 1 |
| 13 | Molecular adaptations un- derlying susceptibility and resistance to social defeat in brain re- ward regions 显示文摘 | Krishnan V Hart MH Graham DL | 2007 | Cell2007，131，： | 1 |
| 14 | Hyperglycemia cxacerbates muscle protein catabolism in bum-injured patients显示文摘 | Gore DC Chinkes DL Hart DW | 2002 | Crit Care Med2002，30，11： | 1 |
| 15 | Centralization phenomenon as a prognostic factor for chronic low back pain and disability显示文摘 | Werneke M Hart DL | 2001 | Spine2001，26，： | 1 |
| 16 | Determinants of skeletal muscle catabolism after severe burn显示文摘 | Hart DW Wolf SE Chinkes DL | | 0，，04： | 1 |
| 17 | Centralization phenomenon as a prognostic factor for chronic low back pain and disability 显示文摘 | Werneke M Hart DL | 2001 | Spine2001，26，： | 1 |
| 18 | Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients显示文摘 | Gore DC Chinkes DL Hart DW | | 0，，12： | 1 |
| 19 | Simulation and new learning technologies显示文摘 | Issenberg SB Gordon MS Gordon DL Safford RE Hart IR | 2001 | Med Teach2001，231，： | 1 |
| 20 | Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neurofilament protein neurofilament-H显示文摘 | Dong DL Xu ZS Hart GW | 1996 | J Biol Chem1996，271，20： | 1 |
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