| 1. |
- Karlsson, Richard, et al.
(författare)
-
Phosphatidylinositol 3-kinase is essential for kit ligand-mediated survival, whereas interleukin-3 and flt3 ligand induce expression of antiapoptotic Bcl-2 family genes
- 2003
-
Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 74:5, s. 923-931
-
Tidskriftsartikel (refereegranskat)abstract
- Cytokines such as interleukin 3 (IL-3), kit ligand (KL), and flt3 ligand (FL) promote survival of hematopoietic stem cells and myeloid progenitor cells. In many cell types, members of the Bcl-2 gene family are major regulators of survival, but the mediating mechanisms are not fully understood. Using two myeloid progenitor cell lines, FDCP-mix and FDC-P1, as well as primary mouse bone marrow progenitors, we demonstrate that KL-mediated survival is dependent on the activation of phosphatidylinositol-3 (PI-3) kinase. The inhibitor LY294002 was able to completely abolish survival mediated by KL, whereas IL-3 and FL were only partially affected. Although all three cytokines induced phosphorylation of protein kinase B (PKB), only KL required PI-3 kinase activity to elicit survival in hematopoietic progenitors. In contrast, pretreatment of cells with inhibitors to the MAP kinase pathway did not affect the survival. We next established if IL-3 and FL activated antiapoptotic Bcl-2 and the related genes Bcl-X-L and Mcl-1. By RNA protection assay and Western blot analysis, we show that all three genes are induced by IL-3, whereas FL induces Bcl-2 and to some extent Bcl-XL. Importantly, KL could not sustain their expression. Moreover, use of inhibitors implied that IL-3 was mainly exerting its effect on Bcl-2 at the level of transcription. The addition of LY294002 did not affect the expression of Bcl-2 and Bcl-XL, and thus, we conclude that expression of antiapoptotic Bcl-2 family member genes is not dependent on PI-3 kinase activity. Our results indicate that cytokines exert distinct survival effects and that FL and IL-3 are capable of sustaining progenitor survival by upregulating the expression of Bcl-2 and related genes.
|
|
| 2. |
- Egermayer, Monica, et al.
(författare)
-
Gels of hydrophobically modified ethyl (hydroxyethyl) cellulose cross-linked by amylose: Effects of hydrophobe architecture
- 2004
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 20:6, s. 2208-2214
-
Tidskriftsartikel (refereegranskat)abstract
- Previous work has shown that amylose (AM) can cross-link hydrophobically modified polymers by inclusion complexation, whereby thermoreversible cold-setting gels are formed. Here we investigate the complexation of AM with different samples of hydrophobically modified ethyl(hydroxyethyl) cellulose (HMEHEC), distinguished by differences in the architecture of the hydrophobes (the hydrophobic side chains). All hydrophobes, except one, were based on linear alkyl chains, but with varying chain lengths (C-12-C-14). In addition, some samples contained short hydrophilic "spacers", consisting of 2-5 ethylene oxide units, between the alkyl chains and the EHEC backbone. Gels of varying strength were obtained for the different AM/HMEHEC samples. The alkyl chain length seemed to be the major factor affecting the gel strength, with longer alkyl chains giving stronger gels. For similar alkyl chain lengths, stronger gels were obtained when a spacer was present. Addition of AM caused a small increase of the cloud points of HMEHECs with C-14 hydrophobes in water. Time-dependent effects and effects of the sample preparation procedure were also investigated. The reversibility of the gelation with respect to shear was confirmed. A gel destroyed by added surfactant was shown to reform on removal of the surfactant by dialysis.
|
|
| 3. |
- Karlberg, Maria, et al.
(författare)
-
Mixed solutions of hydrophobically modified graft and block copolymers
- 2004
-
Ingår i: Colloids and Surfaces A: Physicochemical and Engineering Aspects. - : Elsevier BV. - 0927-7757. ; 236:1-3, s. 159-164
-
Tidskriftsartikel (refereegranskat)abstract
- Phase separation temperatures and viscosities of dilute and semidilute aqueous mixtures of hydrophobically modified graft and block copolymers have been studied. The graft copolymer was hydrophobically modified ethyl(hydroxyethyl)cellulose (HM-EHEC), and the block copolymers were hydrophobically modified poly(ethylene glycol) (HM-PEG) with diblock (DB) or triblock (TB) structures, i.e., modified at one or both ends, respectively. For comparison, viscosity measurements were made also on mixtures of TB with HM-HEC, and on systems where one of the polymers was unmodified (i.e. HM-EHEC/PEG or TB/EHEC). All results indicate mixed hydrophobic associations between graft and block copolymers. Moderate viscosity enhancements were found on addition of HM-PEG to HM-EHEC, and the effects were larger for TB than for DB. The viscosity changes were quite sensitive to the concentration of HM-EHEC. (C) 2004 Elsevier B.V. All rights reserved.
|
|
| 4. |
- Sköld, Maria, 1976, et al.
(författare)
-
Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.
- 2004
-
Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 17:12, s. 1697-705
-
Tidskriftsartikel (refereegranskat)abstract
- Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time.
|
|
| 5. |
- Sköld, Maria, 1976, et al.
(författare)
-
Studies on the autoxidation and sensitizing capacity of the fragrance chemical linalool, identifying a linalool hydroperoxide.
- 2002
-
Ingår i: Contact dermatitis. - 0105-1873. ; 46:5, s. 267-72
-
Tidskriftsartikel (refereegranskat)abstract
- Fragrances are among the most common causes of allergic contact dermatitis. The two monoterpenes linalool and d-limonene are the most frequently incorporated fragrance chemicals in scented products. Previous studies on d-limonene show that this monoterpene oxidizes on air exposure (autoxidation) and that allergenic oxidation products are formed. Due to structural similarities, linalool might also form allergenic oxidation products on air exposure. The aim of the present study was to study the autoxidation of linalool and to investigate the sensitizing potential of linalool before and after air exposure. Linalool was oxidized for 10 weeks and gas chromatographic analyses showed that the content of linalool decreased to about 80%. The chromatograms revealed the formation of other compounds during oxidation. One of the major oxidation products was isolated and identified as 7-hydroperoxy-3,7-dimethyl-octa-1,5-diene-3-ol. This substance is, to the best of our knowledge, described for the first time. In sensitization studies in guinea pigs, linalool of high purity gave no reactions, while linalool that had been oxidized for 10 weeks sensitized the animals. It is concluded that autoxidation of linalool is essential for its sensitizing potential.
|
|
