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- Asker, Noomi, 1968, et al.
(författare)
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Dimerization of the human MUC2 mucin in the endoplasmic reticulum is followed by a N-glycosylation-dependent transfer of the mono- and dimers to the Golgi apparatus.
- 1998
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 273:30, s. 18857-63
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Tidskriftsartikel (refereegranskat)abstract
- Pulse-chase experiments in the colon cell line LS 174T combined with subcellular fractionation by sucrose density gradient centrifugation showed that the initial dimerization of the MUC2 apomucin started directly after translocation of the apomucin into the rough endoplasmic reticulum as detected by calnexin reactivity. As the mono- and dimers were chased, O-glycosylated MUC2 mono- and dimers were precipitated using an O-glycosylation-insensitive antiserum against the N-terminal domain of the MUC2 mucin. These O-glycosylated species were precipitated from the fractions that comigrated with the galactosyltransferase activity during the subcellular fractionation, indicating that not only MUC2 dimers but also a significant amount of monomers are transferred into the Golgi apparatus. Inhibition of N-glycosylation with tunicamycin treatment slowed down the rate of dimerization and introduced further oligomerization of the MUC2 apomucin in the endoplasmic reticulum. Results of two-dimensional gel electrophoresis demonstrated that these oligomers (putative tri- and tetramers) were stabilized by disulfide bonds. The non-N-glycosylated species of the MUC2 mucin were retained in the endoplasmic reticulum because no O-glycosylated species were precipitated after inhibition by tunicamycin. This suggests that N-glycans of MUC2 are necessary for the correct folding and dimerization of the MUC2 mucin.
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| 3. |
- Asker, Noomi, 1968, et al.
(författare)
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Human MUC5AC mucin dimerizes in the rough endoplasmic reticulum, similarly to the MUC2 mucin.
- 1998
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Ingår i: The Biochemical journal. - 0264-6021. ; 335:2, s. 381-7
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Tidskriftsartikel (refereegranskat)abstract
- Biosynthetic studies on the human MUC5AC mucin were performed by immunoprecipitations with antisera recognizing only the non-O-glycosylated apomucin in the colon adenocarcinoma cell line LS 174T. Pulse-chase studies and subcellular fractionations showed that MUC5AC formed dimers in the rough endoplasmic reticulum within 15 min of the initiation of biosynthesis. No non-O-glycosylated species larger than dimers were identified. The dimerization was N-glycosylation-dependent, because tunicamycin treatment significantly lowered the rate of dimerization. When the biosynthesis of MUC5AC apomucin was compared with that of MUC2 apomucin, also produced in the LS 174T cell line, both apomucins were assembled in similar ways with respect to their rates of dimerization with and without inhibition of N-glycosylation. No heterodimerization was observed between the human MUC5AC and the MUC2 apomucins despite the extensive sequence similarities in the positions of the cysteine residues in the C-termini proposed to be involved in mucin dimerization.
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- Olofsson, Gunnar, 1951
(författare)
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Urinary diversion by the Kock ileal reservoir. Studies on clinical outcome, quality of life, bile acid and vitamin B12 metabolism
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Urinary diversion with the Kock ileal reservoir has been performed at Sahlgrenska University Hospital since 1975. One key question is the long-term consequences regarding glomerular filtration rate (GFR) and quality of life of this kind of surgery. Other important topics are the consequences due to loss of ileum.Aims of the study: To analyze the long-term clinical outcome and impact on quality of life in patients with a Kock ileal reservoir. To determine the influence on GFR, bile acid metabolism and bowel habits. To analyze the influence on vitamin B12 metabolism. To develop a method for in vitro determination of bile acid uptake in intestinal mucosa and to determine the site of this uptake. Patients: 176 patients operated on during the period 1975-1999 were included in the study. 122 patients were alive at the time of follow-up. Sub-groups of patients were investigated with regard to quality of life (QOL), bowel habits, bile acid and vitamin B12 metabolism. In vitro mucosal biopsies were obtained at endoscopy or open surgery in patients without known bowel dysfunction. Methods: 70 cm of the distal ileum was used for the creation of the continent reservoir. QOL was assessed with SF-36 and OAS, GFR with chrom-EDTA-clearance, bile acid absorption with the SeHCAT retention test and vitamin B12 uptake with the standard Schilling test. Bile acid uptake in mucosal biopsies was determined using in vitro incubation techniques in forceps biopsies obtained from different parts of the bowel. Results: 90% have a reservoir that functions well. The health status is influenced more by the underlying disease than by the fact that the patient has a continent reservoir. Patients operated for benign functional or inflammatory disease seem to adapt less well to a life with ostomy. Renal function is not impaired by the continent urinary diversion. Most patients have fairly normal bowel habits. One-third of the patients develop post-operative bile acid malabsorption and some patients have severe problems with diarrhoea due to this malabsorption. Continent urinary diversion does not in itself lead to vitamin B12 deficiency. 10% of the patients develop true vitamin B12 deficiency. Substitution is advisable when serum levels of vitamin B12 are below 200 pmol/l. Bile acid uptake in human intestine can be measured with small mucosal biopsies obtained during colonoscopy or open surgery. Bile acids are not only absorbed in the distal ileum but also to a considerable degree 100 cm proximal to the ileocaecal valve. Conclusions: The long-term functional result of continent urinary diversion with a Kock ileal reservoir is good. Patient acceptance is high, and the quality of life is influenced more by the underlying disease. Resection of 70 cm of the distal ileum impairs bile acid absorption. The operation does not per se lead to vitamin B12 deficiency. The Kock ileal reservoir retains its place in the therapeutic arsenal. Small mucosal biopsies can be used for the evaluation of the bile acid uptake in patients with various conditions. Key words: Kock reservoir, urinary diversion, quality of life, bile acids, vitamin B12.
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