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21.
The function of caveolae is hotly debated. It now seems clear that caveolae are stable membrane domains that are kept in place by the actin cytoskeleton. However, this stability can be perturbed, leading to caveolar internalization. Caveolae are important in the regulation of various signaling processes, such as nitric oxide activity, and in cholesterol efflux and cholesterol-ester uptake. Caveolin deficiency particularly affects the cardiovascular system and the lungs but, because the knockout mice are viable, none of the proposed functions appears to be essential. Rather than having a specific function, caveolae might be considered to be multifunctional organelles with a physiological role that varies depending on cell type and cellular needs. 相似文献
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Roepstorff C Vistisen B Roepstorff K Kiens B 《American journal of physiology. Endocrinology and metabolism》2004,287(4):E696-E705
In the present study, we investigated possible sites of regulation of long-chain fatty acid (LCFA) oxidation in contracting human skeletal muscle. Leg plasma LCFA kinetics were determined in eight healthy men during bicycling (60 min, 65% peak oxygen uptake) with either high (H-FOX) or low (L-FOX) leg fat oxidation (H-FOX: 1,098 +/- 140; L-FOX: 494 +/- 84 micromol FA/min, P < 0.001), which was achieved by manipulating preexercise muscle glycogen (H-FOX: 197 +/- 21; L-FOX: 504 +/- 25 mmol/kg dry wt, P < 0.001). Several blood metabolites and hormones were kept nearly similar between trials by allocating a preexercise meal and infusing glucose intravenously during exercise. During exercise, leg plasma LCFA fractional extraction was identical between trials (H-FOX: 17.8 +/- 1.6; L-FOX: 18.2 +/- 1.8%, not significant), suggesting similar LCFA transport capacity in muscle. On the contrary, leg plasma LCFA oxidation was 99% higher in H-FOX than in L-FOX (421 +/- 47 vs. 212 +/- 37 micromol/min, P < 0.001). Probably due to the slightly higher (P < 0.01) plasma LCFA concentration in H-FOX than in L-FOX, leg plasma LCFA uptake was nonsignificantly (P = 0.17) higher (25%) in H-FOX than in L-FOX, yet the fraction of plasma LCFA uptake oxidized was 61% higher (P < 0.05) in H-FOX than in L-FOX. Accordingly, the muscle content of several lipid-binding proteins did not differ significantly between trials, although fatty acid translocase/CD36 and caveolin-1 were elevated (P < 0.05) by the high-intensity exercise and dietary manipulation allocated on the day before the experimental trial. The present data suggest that, in contracting human skeletal muscle with different fat oxidation rates achieved by manipulating preexercise glycogen content, transsarcolemmal transport is not limiting plasma LCFA oxidation. Rather, the latter seems to be limited by intracellular regulatory mechanisms. 相似文献
23.
Philip Juul Pedersen Kirsten Brolin Thomsen Emma Rie Olander Frank Hauser Maria de los Angeles Tejada Kristian Lundgaard Poulsen Soren Grubb Rikke Buhl Kirstine Calloe Dan Arne Klaerke 《PloS one》2015,10(9)
The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death—conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE and conventional PCR on mRNA purified from equine myocardial tissue. Equine KV11.1 and KCNE2 cDNA had a high homology to human genes (93 and 88%, respectively). Equine and human KV11.1 and KV11.1/KCNE2 were expressed in Xenopus laevis oocytes and investigated by two-electrode voltage-clamp. Equine KV11.1 currents were larger compared to human KV11.1, and the voltage dependence of activation was shifted to more negative values with V1/2 = -14.2±1.1 mV and -17.3±0.7, respectively. The onset of inactivation was slower for equine KV11.1 compared to the human homolog. These differences in kinetics may account for the larger amplitude of the equine current. Furthermore, the equine KV11.1 channel was susceptible to pharmacological block with terfenadine. The physiological importance of KV11.1 was investigated in equine right ventricular wedge preparations. Terfenadine prolonged action potential duration and the effect was most pronounced at slow pacing. In conclusion, these findings indicate that horses could be disposed to both congenital and acquired LQTS. 相似文献
24.
Xue Lin Jan Stenvang Mads Heilskov Rasmussen Shida Zhu Niels Frank Jensen Line S Tarpgaard Guangxia Yang Kirstine Belling Claus Lindbjerg Andersen Jian Li Lars Bolund Nils Brünner 《BMC genomics》2015,16(1)
Background
Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown.Results
We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38 or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of ‘DNA methylation entropy’ to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples.Conclusion
Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1552-y) contains supplementary material, which is available to authorized users. 相似文献25.
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Morten Dall Kirstine Calloe Martin Haupt-Jorgensen Jesper Larsen Nicole Schmitt Knud Josefsen Karsten Buschard 《PloS one》2013,8(6)
In non-obese diabetic (NOD) mice, diabetes incidence is reduced by a gluten-free diet. Gluten peptides, such as the compound gliadin, can cross the intestinal barrier and may directly affect pancreatic beta cells. We investigated the effects of enzymatically-digested gliadin in NOD mice, INS-1E cells and rat islets. Six injections of gliadin digest in 6-week-old NOD mice did not affect diabetes development, but increased weight gain (20% increase by day 100). In INS-1E cells, incubation with gliadin digest induced a dose-dependent increase in insulin secretion, up to 2.5-fold after 24 hours. A similar effect was observed in isolated rat islets (1.6-fold increase). In INS-1E cells, diazoxide reduced the stimulatory effect of gliadin digest. Additionally, gliadin digest was shown to decrease current through KATP-channels. A specific gliadin 33-mer had a similar effect, both on current and insulin secretion. Finally, INS-1E incubation with gliadin digest potentiated palmitate-induced insulin secretion by 13% compared to controls. Our data suggest that gliadin fragments may contribute to the beta-cell hyperactivity observed prior to the development of type 1 diabetes. 相似文献
28.
Josephine Geertsen Keller Kirstine Mejlstrup Hymller Maria Eriksen Thorsager Noriko
Y Hansen Jens
Uldum Erlandsen Cinzia Tesauro Anne
Katrine
W Simonsen Anne
Bech Andersen Kamilla Vands
Petersen Lise
Lolle Holm Magnus Stougaard Brage
Storstein Andresen Peter Kristensen Rikke Frhlich Birgitta
R Knudsen 《Nucleic acids research》2022,50(11):6332
29.
Ildiko Lingvay Kirstine Brown-Frandsen Helen M. Colhoun John Deanfield Scott S. Emerson Sille Esbjerg Søren Hardt-Lindberg G. Kees Hovingh Steven E. Kahn Robert F. Kushner A. Michael Lincoff Steven P. Marso Tea Monk Fries Jorge Plutzky Donna H. Ryan the SELECT Study Group 《Obesity (Silver Spring, Md.)》2023,31(1):111-122
30.
Westergaard UB Sørensen ES Hermey G Nielsen MS Nykjaer A Kirkegaard K Jacobsen C Gliemann J Madsen P Petersen CM 《The Journal of biological chemistry》2004,279(48):50221-50229
A Vps10p domain makes up the entire luminal part of Sortilin, and this type of domain is the hallmark of a new family of neuronal receptors that target a variety of ligands, including neurotrophins and neuropeptides. We have shown that two structural features of the Vps10p domain, the N-terminal propeptide and the C-terminal segment of ten conserved cysteines (10CC), are key elements in the function of Sortilin. The propeptide has two functions. (i) It binds the mature part of Sortilin and prevents ligands in the biosynthetic pathway from binding to the uncleaved proreceptor, and (ii) it facilitates receptor transport in early Golgi compartments by a mechanism that does not depend on its ability to prevent ligand binding. In contrast, other Vps10p domain receptors, such as SorLA and SorCS3, do not need their propeptide for normal and swift processing. The 10CC segment constitutes an exchangeable module containing five conserved disulfide bridges, and using module-shuffling and truncations, we have shown that the 10CC segment is a major ligand-binding region in Sortilin. 相似文献