| 1. |
- Li, Lu, 1964, et al.
(författare)
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Epigallocatechin gallate increases the formation of cytosolic lipid droplets and decreases the secretion of apoB-100 VLDL
- 2006
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Ingår i: J Lipid Res. - 0022-2275. ; 47:1, s. 67-77
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Tidskriftsartikel (refereegranskat)abstract
- Epigallocatechin gallate (EGCG) increases the formation of cytosolic lipid droplets by a mechanism that is independent of the rate of triglyceride biosynthesis and involves an enhanced fusion between lipid droplets, a process that is crucial for their growth in size. EGCG treatment reduced the secretion of both triglycerides and apolipoprotein B-100 (apoB-100) VLDLs but not of transferrin, albumin, or total proteins, indicating that EGCG diverts triglycerides from VLDL assembly to storage in the cytosol. This is further supported by the observed increase in both intracellular degradation of apoB-100 and ubiquitination of the protein (indicative of increased proteasomal degradation) in EGCG-treated cells. EGCG did not interfere with the microsomal triglyceride transfer protein, and the effect of EGCG on the secretion of VLDLs was found to be independent of the LDL receptor. Thus, our results indicate that EGCG promotes the accumulation of triglycerides in cytosolic lipid droplets, thereby diverting lipids from the assembly of VLDL to storage in the cytosol. Our results also indicate that the accumulation of lipids in the cytosol is not always associated with increased secretion of VLDL.
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| 2. |
- Beck, Caroline, 1976
(författare)
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Assembly and Secretion of Atherogenic Lipoproteins
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The classical dyslipidemia seen in patients with type 2 diabetes is characterized by elevated serum triglycerides (TG), low levels of high-density lipoprotein cholesterol and the appearance of small, dense low-density lipoproteins (LDL). It is now recognized that the different components of diabetic dyslipidemia are not isolated abnormalities but are closely linked to each other metabolically, and are initiated by the hepatic overproduction of large triglyceride-rich very low-density lipoproteins (VLDL1). Diabetic dyslipidemia frequently precedes type 2 diabetes by several years, indicating that the disturbance of lipid metabolism is an early event in the development of cardiovascular complications of type 2 diabetes. It is thus of key importance to elucidate the mechanisms involved in the production of VLDL1. The aim of this thesis was to further clarify the molecular mechanisms of the assembly process and secretion of apolipoprotein B (apoB)-containing lipoproteins. The results indicate that apoB100 assembles into partially lipidated dense pre-VLDL that is retained in the cell unless further converted into VLDL2 by size-dependent lipidation. VLDL2 in turn can proceed through the secretory pathway to be secreted or converted to VLDL1 in the second step of the assembly. Furthermore, an efficient formation of VLDL1 specifically requires a sequence located between apoB46.8 and apoB48. This sequence interacts with the B-cell receptor-associated protein (BAP31), which seems essential for an efficient secretion of VLDL1, but not for the secretion of denser particles. The formation of lipoproteins depends on the availability of lipids. However, the results show that the accumulation of cytoplasmic lipids is not directly associated with increased secretion of VLDL. The phenol epicallocatehin gallate (EGCG) diverts TG from the secretory pathway for storage in cytosolic lipid droplets. While increasing the cytosolic lipid droplet fusion rate and TG content in the cytsosol, apoB100 secretion from the cells is decreased. As a consequence, apoB becomes degraded. The results presented advance our understanding of the complex mechanisms underlying the formation of VLDL. Clarification of these molecular mechanisms will hopefully enable development of targeted treatment for diabetic dyslipidemia, which is of key importance given the high risk for coronary vascular disease (CVD) in patients with type 2 diabetes and the metabolic syndrome.
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| 3. |
- Beck, Caroline, 1976, et al.
(författare)
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Tissue-specific targeting for cardiovascular gene transfer. Potential vectors and future challenges
- 2004
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Ingår i: Current Gene Therapies. - 1566-5232. ; 4:4, s. 457-67
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of genes to cardiovascular cells in vivo remains the major challenge for current gene therapy modalities. However, recent developments in retargeting adenoviral vectors are promising to improve transduction efficiency in the cardiovascular cells. After systemic application, most adenoviral vectors are trapped by the liver, hampering delivery to target cardiovascular tissues. Furthermore, a majority of vectors for vascular gene transfer utilizes strong heterologous viral promoters, such as CMV. A potential side effect related to the use of such vectors is the systemic organ toxicity resulting from unrestricted transgene expression. These vectors have the additional problem of being frequently shut-down in vivo. Therefore, both retargeting adenoviral vectors and the use of tissue-specific promoter-driven vectors offer an enhanced safety profile by reducing ectopic expression in vital organs including the liver and lung. However, the limiting factor for the use of tissue-specific promoters is the low-level of expression compared with their viral counterparts. Both the development of efficient and strong vectors using cell-specific regulatory elements and the production of therapeutic proteins at sufficient levels is urgently needed to inhibit vasculoproliferative disorders. This review will focus on some of the recent achievements in vector development relevant to the delivery of vascular gene therapies targeted to the vascular endothelium, smooth muscle cells and macrophages during arterial remodelling.
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| 4. |
- Petelenz-Kurdziel, Elzbieta, et al.
(författare)
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Quantification of cell volume changes upon hyperosmotic stress in Saccharomyces cerevisiae.
- 2011
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Ingår i: Integrative biology : quantitative biosciences from nano to macro. - : Oxford University Press (OUP). - 1757-9708 .- 1757-9694. ; 3:11, s. 1120-6
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Tidskriftsartikel (refereegranskat)abstract
- Cell volume is a biophysical property, which is of great importance for quantitative characterisations of biological processes, such as osmotic adaptation. It also is a crucial parameter in the most common type of mathematical description of cellular behaviour-ordinary differential equation (ODE) models, e.g. the integrative model of the osmotic stress response in baker's yeast (E. Klipp, B. Nordlander, R. Kruger, P. Gennemark and S. Hohmann, Nat. Biotechnol., 2005, 23, 975-982). Until recently only rough estimates of this value were available. In this study we measured the mean volume of more than 300 individual yeast cells (Saccharomyces cerevisiae). We quantitatively characterised the dependence between the relative cell volume and the concentration of osmoticum in the cell surrounding. We also followed the recovery of the cellular volume over time, as well as the influence of increased external osmolarity on the nuclear volume. We found that cell shrinkage caused by shifts in the external osmolarity is proportional to the stress intensity only up to 1000 mM NaCl. At this concentration the yeast cells shrink to approximately 55% of their unstressed volume and this volume is maintained even in the case of further osmolarity increase. We observed that returning to the initial, unstressed volume takes more than 45 minutes for stress concentrations exceeding 100 mM NaCl and that only cells treated with the latter concentration are able to fully regain their initial size within the course of the experiment. We postulate that the cytoplasm plays a protective role for the nucleus by buffering the changes in volume caused by external osmolarity shifts. In conclusion, we quantitatively characterised the dynamics of cell volume changes caused by hyperosmotic stress, providing an accurate description of a biophysical cell property, which is crucial for precise mathematical simulations of cellular processes.
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| 5. |
- Stillemark-Billton, Pia, 1968, et al.
(författare)
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Relation of the size and intracellular sorting of apoB to the formation of VLDL 1 and VLDL 2
- 2005
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Ingår i: J Lipid Res. - 0022-2275. ; 46:1, s. 104-14
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we tested the hypothesis that two separate pathways, the two-step process and an apolipoprotein B (apoB) size-dependent lipidation process, give rise to different lipoproteins. Expression of apoB-100 and C-terminally truncated forms of apoB-100 in McA-RH7777 cells demonstrated that VLDL particles can be assembled by apoB size-dependent linear lipidation, resulting in particles whose density is inversely related to the size of apoB. This lipidation results in a LDL-VLDL 2 particle containing apoB-100. VLDL 1 is assembled by the two-step process by apoB-48 and larger forms of apoB but not to any significant amount by apoB-41. The major amount of intracellular apoB-80 and apoB-100 banded with a mean density of 1.10 g/ml. Its formation was dependent on the sequence between apoB-72 and apoB-90. This dense particle, which is retained in the cell, possibly by chaperones or association with the microsomal membrane, is a precursor of secreted VLDL 1. The intracellular LDL-VLDL 2 particles formed during size-dependent lipidation appear to be the precursors of intracellular VLDL 1. We propose that the dense apoB-100 intracellular particle is converted to LDL-VLDL 2 by size-dependent lipidation. LDL-VLDL 2 is secreted or converted to VLDL 1 by the uptake of the major amount of triglycerides.
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| 6. |
- Volpe, Giovanni, 1979, et al.
(författare)
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Roadmap for optical tweezers
- 2023
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Ingår i: Journal of Physics-Photonics. - : IOP Publishing. - 2515-7647. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects, ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in the life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nano-particle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration.
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| 7. |
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