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| 2. |
- Johnson, Magnus S.C. 1969, et al.
(författare)
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Interaction of scavenger receptor class B type I with peroxisomal targeting receptor Pex5p.
- 2003
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Ingår i: Biochemical and biophysical research communications. - 0006-291X. ; 312:4, s. 1325-34
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Tidskriftsartikel (refereegranskat)abstract
- Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective HDL lipid uptake. Peroxisomes play an important role in lipid metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p. We have previously identified a PTS1 motif in the intracellular domain of rat SR-BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the peroxisome as demonstrated by double labeling with anti-Flag IgG and anti-catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However, when an antibody against Pex5p was used for immunoprecipitation, only the 57kDa, non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in vitro.
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| 3. |
- Lagerström, Malin C., et al.
(författare)
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High affinity agonistic metal ion binding sites within the melanocortin 4 receptor illustrate conformational change of transmembrane region 3
- 2003
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 278:51, s. 51521-51526
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Tidskriftsartikel (refereegranskat)abstract
- We created a molecular model of the human melanocortin 4 receptor (MC4R) and introduced a series of His residues into the receptor protein to form metal ion binding sites. We were able to insert micromolar affinity binding sites for zinc between transmembrane region (TM) 2 and TM3 where the metal ion alone was able to activate this peptide binding G-protein-coupled receptor. The exact conformation of the metal ion interactions allowed us to predict the orientation of the helices, and remodeling of the receptor protein indicated that Glu100 and Ile104 in TM2 and Asp122 and Ile125 in TM3 are directed toward a putative area of activation of the receptor. The molecular model suggests that a rotation of TM3 may be important for activation of the MC4R. Previous models of G-protein-coupled receptors have suggested that unlocking of a stabilizing interaction between the DRY motif, in the cytosolic part of TM3, and TM6 is important for the activation process. We suggest that this unlocking process may be facilitated through creation of a new interaction between TM3 and TM2 in the MC4R.
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| 4. |
- Larsson, Susanna C, et al.
(författare)
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Dietary long-chain n-3 fatty acids for the prevention of cancer : a review of potential mechanisms
- 2004
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 79:6, s. 935-45
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence from animal and in vitro studies indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit carcinogenesis. The epidemiologic data on the association between fish consumption, as a surrogate marker for n-3 fatty acid intake, and cancer risk are, however, somewhat less consistent. This review highlights current knowledge of the potential mechanisms of the anticarcinogenic actions of n-3 fatty acids. Moreover, a possible explanation of why some epidemiologic studies failed to find an association between n-3 fatty acid intake and cancer risk is provided. Several molecular mechanisms whereby n-3 fatty acids may modify the carcinogenic process have been proposed. These include suppression of arachidonic acid-derived eicosanoid biosynthesis; influences on transcription factor activity, gene expression, and signal transduction pathways; alteration of estrogen metabolism; increased or decreased production of free radicals and reactive oxygen species; and mechanisms involving insulin sensitivity and membrane fluidity. Further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n-3 fatty acid intake on cancer risk.
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| 5. |
- Mandic, Aleksandra, et al.
(författare)
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Cisplatin induces the proapoptotic conformation of Bak in a deltaMEKK1-dependent manner
- 2001
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 21:11, s. 3684-3691
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Tidskriftsartikel (refereegranskat)abstract
- In a panel of four human melanoma cell lines, equitoxic doses of cisplatin induced the proapoptotic conformation of the Bcl-2 family protein Bak prior to the execution phase of apoptosis. Because cisplatin-induced modulation of the related Bax protein was seen in only one cell line, a degree of specificity in the signal to Bak is indicated. Little is known about upstream regulation of Bak activity. In this study, we examined whether the apoptosis-specific pathway mediated by a kinase fragment of MEKK1 (DeltaMEKK1) is involved in the observed Bak modulation. We report that expression of a kinase-inactive fragment of MEKK1 (dominant negative MEKK [dnMEKK]) efficiently blocked cisplatin-induced modulation of Bak and cytochrome c release and consequently also reduced DEVDase activation and nuclear fragmentation. Accordingly, expression of a kinase-active MEKK1 fragment (dominant positive MEKK) was sufficient to induce modulation of Bak in three cell lines and to induce apoptosis in two of these. dnMEKK did not block cisplatin-induced c-Jun N-terminal kinase (JNK) activation, in agreement with a specifically proapoptotic role for the DeltaMEKK1 pathway. Finally, we show that reduction of Bak expression by antisense Bak reduced cisplatin-induced loss of mitochondrial integrity and caspase cleavage activity in breast cancer cell lines. In summary, we have identified Bak as a cisplatin-regulated component downstream in a proapoptotic, JNK-independent DeltaMEKK1 pathway.
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| 7. |
- Svane, Maria, 1957, et al.
(författare)
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Chemical analysis of individual alkali-containing aerosol particles: Design and performance of a surface ionization particle beam mass spectrometer
- 2004
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 38:7, s. 655-663
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Tidskriftsartikel (refereegranskat)abstract
- A mobile particle beam mass spectrometer has been developed to measure the alkali metal content in individual submicron aerosol particles. The instrument employs an aerodynamic inlet system for efficient sampling of particles into vacuum, and the detection of individual particles is based on decomposition and surface ionization on a hot platinum surface. A boxlike design of the hot ionizing surface is shown to limit problems associated with particle bounce effects and incomplete ionization, and the decomposition/ionization process is not sensitive to detailed particle properties. High transmission efficiencies and quantitative determination of the alkali metal content in individual particles with diameters down to 14 nm are demonstrated. Experiments with particles doped with alkali salt show that the size range may be extended down to a few nanometers after further improvements of the inlet system. High size resolution can be achieved with the instrument for particle sizes down to tens of nanometers, as illustrated by the detection of multiply charged particles passing through a DMA. The robustness of the instrument makes it suitable for field measurement applications, and the technique is demonstrated at a 12 MW biomass combustion facility. The performance of the instrument and further refinements of the technique are discussed, and potential applications in field and laboratory studies are outlined.
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