| 1. |
|
|
| 2. |
|
|
| 3. |
- Godl, Klaus, et al.
(author)
-
The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment.
- 2002
-
In: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 277:49, s. 47248-56
-
Journal article (peer-reviewed)abstract
- The N terminus of the human MUC2 mucin (amino acids 1-1397) has been expressed as a recombinant tagged protein in Chinese hamster ovary cells. The intracellular form was found to be an endoglycosidase H-sensitive monomer, whereas the secreted form was an oligomer that gave monomers upon disulfide bond reduction. The secreted MUC2 N terminus contained a trypsin-resistant core fragment. Edman sequencing and mass spectrometry of the peptides obtained localized this core fragment to the C-terminal end of the recombinant protein. This core retained its oligomeric nature with an apparent mass of approximately 240 kDa. Upon reduction, peptides of approximately 85 kDa were found, suggesting that the N terminus forms trimers. This interpretation was also supported by gel electrophoresis and gel filtration of the intact MUC2 N terminus. Electron microscopy revealed three globular domains each linked via an extended and flexible region to a central part in a trefoil-like manner. Immunostaining with gold-labeled antibodies localized the N-terminal end to the three globular structures, and the antibodies directed against the Myc and green fluorescent protein tags attached at the C terminus localized these to the stalk side of the central trefoil. The N terminus of the MUC2 mucin is thus assembled into trimers that contain proteolytically stable parts, suggesting that MUC2 can only be partly degraded by intestinal proteases and thus is able to maintain a mucin network protecting the intestine.
|
|
| 4. |
- Hansson, Gunnar C., 1951, et al.
(author)
-
Biosynthesis and Secretion of Mucins, Especially the MUC2 Mucin, in Relation to Cystic Fibrosis
- 2005
-
In: Advances in Experimental Medicine and Biology. - Göteborg : Springer US. - 9780387230764 ; , s. 169-178
-
Book chapter (other academic/artistic)abstract
- The typical CF symptoms with viscous and trapped mucus are still lacking a full explanation. Here we suggest that the CF mucus become sticky and adherent to the epithelial cells by a covalent attachment of MUC2 and MUC5AC. We also suggest that the expression of MUC2 in the lungs could contribute to the CF phenotype. However, there are several unanswered questions before these suggestions can be proved. Among the most urgent ones are to show to what molecules the generated anhydride can attach or if the anhydride only has been hydrolyzed. Once this and other questions have been answered, one can start to address potential therapeutic approaches using recent advances in mucin knowledge.
|
|
| 5. |
- Hildingh, Cathrine, 1949-, et al.
(author)
-
Stress, health complaints and self-confidence : a comparison between young adult women in Sweden and USA
- 2006
-
In: Scandinavian Journal of Caring Sciences. - Chichester, UK : Wiley-Blackwell. - 0283-9318 .- 1471-6712. ; 20:2, s. 202-208
-
Journal article (peer-reviewed)abstract
- Transition to adulthood is a period in life when women encounter conflicts, ambiguities and rapidly expanding roles that may be stressful and difficult to manage. The aim of this study was to compare stress in daily life, health complaints and self-confidence in 26-year old women in two different cultures. A health survey study was performed among Swedish women (n = 386) and American women (n = 201) living in urban areas at the West coast of Sweden and in Minnesota. Both Swedish and American women reported stress in their everyday life, with higher figures for the Americans. Overall health was rated lower by the Swedish women and they reported more health complaints such as headache, general tiredness, irritability, depression and sleeping disorders. There was a difference between groups in self-confidence with higher figures for excellent self-confidence among American women. However, low self-confidence was reported by more American than Swedish women. A good work situation predicted self-confidence in Swedish women and financial confidence in American women. Physical fitness was associated with self-confidence in both groups. Young women in both cultures experienced high level of stress but health related complaints were more common among Swedish women. High stress and health complaints must be taken seriously and interventions to support young women in the midst of transition to adulthood should contain stress reduction as well as empowerment performed in a more effective way than today in different health care settings and at place of work.
|
|
| 6. |
- Lidell, Martin, 1970, et al.
(author)
-
An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway.
- 2003
-
In: The Journal of biological chemistry. - 0021-9258. ; 278:16, s. 13944-51
-
Journal article (peer-reviewed)abstract
- During purification of a recombinant MUC2 C terminus expressed in CHO-K1 cells, the protein was partly cleaved when buffers with a pH of 6.0 were used. When buffers with higher pH values were used, less cleavage was found. Disulfide bonds held the two fragments generated together as these were only observed after reduction. Edman sequencing of the C-terminal 110-kDa fragment revealed that the cleavage had occurred at an Asp-Pro bond, a site described previously to generate the so-called "link peptide" after disulfide bond reduction. In vitro studies on the conditions for cleavage showed that it occurred in a time-dependent manner at a pH below 6.0. Furthermore, the reaction was not enzyme-mediated as it occurred in pure preparations of the MUC2 C terminus and was not inhibited by protease inhibitors. When expressed in the mucin producing cell line LS 174T, the C terminus was cleaved to a higher extent compared with the CHO-K1 cells. Neutralizing the secretory pathway with either NH(4)Cl or bafilomycin A1 inhibited this cleavage. Altogether, our results suggest that the cleavage is an autocatalytic reaction that occurs in the acidic environment of the late secretory pathway. Furthermore, the cleavage produced a new, reactive C terminus that has the potential to attach the mucin to itself or other molecules. Because a pH below 6 can be reached in the late secretory pathway and on mucosal surfaces, the cleavage and possible cross-linking are likely to be of biological importance.
|
|
| 7. |
- Lidell, Martin, 1970, et al.
(author)
-
The recombinant C-terminus of the human MUC2 mucin forms dimers in Chinese-hamster ovary cells and heterodimers with full-length MUC2 in LS 174T cells.
- 2003
-
In: The Biochemical journal. - 0264-6021. ; 372:Pt 2, s. 335-45
-
Journal article (peer-reviewed)abstract
- The entire cDNA corresponding to the C-terminal cysteine-rich domain of the human MUC2 apomucin, after the serine- and threonine-rich tandem repeat, was expressed in Chinese-hamster ovary-K1 cells and in the human colon carcinoma cell line, LS 174T. The C-terminus was expressed as a fusion protein with the green fluorescent protein and mycTag sequences and the murine immunoglobulin kappa-chain signal sequence to direct the protein to the secretory pathway. Pulse-chase studies showed a rapid conversion of the C-terminal monomer into a dimer in both Chinese-hamster ovary-K1 and LS 174T cells. Disulphide-bond-stabilized dimers secreted into the media of both cell lines had a higher apparent molecular mass compared with the intracellular forms. The MUC2 C-terminus was purified from the spent culture medium and visualized by molecular electron microscopy. The dimer nature of the molecule was visible clearly and revealed that each monomer was attached to the other by a large globular domain. Gold-labelled antibodies against the mycTag or green fluorescent protein revealed that these were localized to the ends opposite to the parts responsible for the dimerization. The C-terminus expressed in LS 174T cells formed heterodimers with the full-length wild-type MUC2, but not with the MUC5AC mucin, normally expressed in LS 174T cells. The homodimers of the MUC2 C-termini were secreted continuously from the LS 174T cells, but no wild-type MUC2 secretion has been observed from these cells. This suggests that the information for sorting the MUC2 mucin into the regulated secretory pathway in cells having this ability is present in parts other than the C-terminus of MUC2.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Pham, T. T., et al.
(author)
-
Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot
- 2020
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:7, s. 2300-2310
-
Journal article (peer-reviewed)abstract
- CONTEXT: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. OBJECTIVE: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). DESIGN: This was a cross-sectional and longitudinal study. SETTING: The study was conducted in a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. INTERVENTION(S): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. MAIN OUTCOME MEASURE: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. RESULTS: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. CONCLUSIONS: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism. © Endocrine Society 2020.
|
|
