| 1. |
- Basic, Vladimir T., 1982-, et al.
(författare)
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TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes
- 2014
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 34:1, s. 228-236
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Tidskriftsartikel (refereegranskat)abstract
- Decreased skeletal muscle capillarization is considered to significantly contribute to the development of pulmonary cachexia syndrome (PCS) and progressive muscle wasting in several chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). It is unclear to which extent the concurrent presence of systemic inflammation contributes to decreased skeletal muscle capillarization under these conditions. The present study was designed to examine in vitro the effects of the pro-inflammatory cytokine, tumor necrosis factor (TNF), on the regulation of hypoxia-angiogenesis signal transduction and capillarization in skeletal muscles. For this purpose, fully differentiated C2C12 skeletal muscle myocytes were stimulated with TNF and maintained under normoxic or hypoxic conditions. The expression levels of the putative elements of the hypoxia-angiogenesis signaling cascade were examined using qPCR, western blot analysis and immunofluorescence. Under normoxic conditinos, TNF stimulation increased the protein expression of anti-angiogenic von-Hippel Lindau (VHL), prolyl hydroxylase (PHD)2 and ubiquitin conjugating enzyme 2D1 (Ube2D1), as well as the total ubiquitin content in the skeletal muscle myocytes. By contrast, the expression levels of hypoxia-inducible factor 1‑α (HIF1-α) and those of its transcriptional targets, vascular endothelial growth factor (VEGF)A and glucose transporter 1 (Glut1), were markedly reduced. In addition, hypoxia increased the expression of the VHL transcript and further elevated the VHL protein expression levels in C2C12 myocytes following TNF stimulation. Consequently, an impaired angiogenic potential was observed in the TNF-stimulated myocytes during hypoxia. In conclusion, TNF increases VHL expression and disturbs hypoxia-angiogenesis signal transduction in skeletal muscle myocytes. The current findings provide a mechanism linking systemic inflammation and impaired angiogenesis in skeletal muscle. This is particularly relevant to further understanding the mechanisms mediating muscle wasting and cachexia in patients with chronic inflammatory diseases, such as COPD.
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| 2. |
- Bilbija, Dusan, et al.
(författare)
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Expression of retinoic acid target genes in coronary artery disease
- 2014
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Ingår i: International Journal of Molecular Medicine. - Athens, Greece : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 33:3, s. 677-86
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Tidskriftsartikel (refereegranskat)abstract
- Coronary atherosclerosis can lead to myocardial infarction, and secondarily to post-infarct remodelling and heart failure. Retinoic acid (RA) influences cell proliferation. We hypothesized that RA could influence gene expression and proliferation of cardiovascular cells. Left ventricular biopsies from patients with end-stage heart failure due to coronary artery disease (CAD) or dilated cardiomyopathy were investigated for the content of RA metabolites using liquid chromatography mass spectrometry (LC-MS/MS), and compared with healthy donors. All-trans retinoic acid (ATRA) was increased in the hearts of CAD patients. Gene expression (quantitative PCR) of RA target genes was not influenced in failing hearts, but was increased in the hearts of patients with CAD undergoing open heart surgery. The expression of RA target genes was increased in atherosclerotic lesions from carotid arteries compared to healthy arteries. Stimulation of cardiomyocytes, cardiofibroblasts, smooth muscle cells and endothelial cells with ATRA increased the gene expression of the key enzymes. Cardiofibroblast and smooth muscle cell proliferation were reduced by ATRA, which increased endothelial cell proliferation. Coronary artery disease leads to increased expression of RA target genes. ATRA accumulated in the failing human heart. All investigated cell types present in the heart had induced expression of RA target genes when stimulated with ATRA, which also influenced cell proliferation.
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| 3. |
- Du, Jian, et al.
(författare)
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Antiproliferative effect of alpinetin in BxPC-3 pancreatic cancer cells
- 2012
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 29:4, s. 607-612
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Tidskriftsartikel (refereegranskat)abstract
- Alpinetin is a novel plant flavonoid derived from Alpinia katsumadai Hayata, found to possess strong anticancer effects. However, the antitumor effect of alpinetin on pancreatic cancer cells and the detailed mechanism remain unclear. The aim of this study was to investigate alpinetin's beneficial effect on pancreatic cancer and the possible molecular mechanism involved. Pancreatic cancer cell lines were treated with alpinetin at various doses and for different times, and the effect of alpinetin on cell growth inhibition, apoptosis and the cell cycle was determined. The expression of Bcl-2, Bcl-xL, XIAP and Bax, the activity of caspases and the levels of cytochrome c released were measured. The results showed that alpinetin inhibited the viability of three pancreatic cancer cell lines and induced apoptosis of BxPC-3 cells in a dose- and time-dependent manner. This was accompanied by regulation of the expression of Bcl-2, Bcl-xL, Bax and XIAP. Furthermore, alpinetin treatment led to the release of cytochrome c and activation of caspases-3, -8 and -9 proteins. Taken together, our studies indicate that alpinetin inhibited the proliferation of pancreatic cancer cells possibly through the regulation of the Bcl-2 family and XIAP expression, release of cytochrome c and the activation of caspases. Alpinetin may serve as a potential agent for the development of pancreatic cancer cell therapies.
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| 4. |
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| 5. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Dietary herring improves plasma lipid profiles and reduces atherosclerosis in obese low-density lipoprotein receptor-deficient mice
- 2012
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 29:3, s. 331-37
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Tidskriftsartikel (refereegranskat)abstract
- Diet is a significant modifiable risk factor for cardiovascular disease and high fish intake has been associated with vascular health in population studies. However, intervention studies have been inconclusive. In this study, male low-density lipoprotein receptor-deficient mice were given 16-week high fat/high sucrose diets, supplemented with either minced herring fillets or minced beef. The diets were matched in total fat and cholesterol content; taurine content and fatty acid composition was analysed. Body weights were recorded throughout the study; plasma lipids were analysed at week 8 and 16. Body composition and adipocyte size were evaluated at study end. Atherosclerosis was evaluated at week 12 (ultrasound) and at termination (en face histology). Herring-fed mice had a higher proportion of long-chain n-3 polyunsaturated fatty acids in the hepatic triacylglycerides (TAG) and phospholipid fractions. The herring-fed mice had increased body weight (P=0.007), and reduced epididymal adipocyte size (P=0.009), despite similar food intake and body composition as the beef-fed mice. The herring-fed mice had lower plasma TAG and very-low-density lipoprotein (VLDL)-cholesterol concentrations throughout the study (TAG; P=0.0012 and 0.004, VLDL-cholesterol; P=0.006 and 0.041, week 8 and 16, respectively). At week 16, the herring-fed had higher plasma concentrations of HDL-cholesterol (P=0.004) and less atherosclerotic lesions in the aortic arch (P=0.007) compared with the beef-fed mice. In conclusion, dietary herring in comparison to beef markedly improved vascular health in this mouse model, suggesting that herring provides an added value beyond its content of macronutrients.
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| 6. |
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| 7. |
- Guaran, Valeria, et al.
(författare)
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Association between idiopathic hearing loss and mitochondrial DNA mutations : a study on 169 hearing-impaired subjects
- 2013
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Ingår i: International Journal of Molecular Medicine. - Athen : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 32:4, s. 785-794
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in mitochondrial DNA (mtDNA) have been shown to be an important cause of sensorineural hearing loss (SNHL). In this study, we performed a clinical and genetic analysis of 169 hearing-impaired patients and some of their relatives suffering from idiopathic SNHL, both familial and sporadic. The analysis of four fragments of their mtDNA identified several polymorphisms, the well known pathogenic mutation, A1555G, and some novel mutations in different genes, implying changes in the aminoacidic sequence. A novel sporadic mutation in 12S rRNA (MT-RNR1), not previously reported in the literature, was found in a case of possible aminoglycoside-induced progressive deafness.
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| 10. |
- Hardell, Lennart, et al.
(författare)
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Exposure to wireless phone emissions and serum beta-trace protein.
- 2010
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Ingår i: International journal of molecular medicine. - : Spandidos Publications. - 1791-244X .- 1107-3756. ; 26:2, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- The lipocalin type of prostaglandin D synthase or beta-trace protein is synthesized in the choroid plexus, lepto-meninges and oligodendrocytes of the central nervous system and is secreted into the cerebrospinal fluid. beta-trace protein is the key enzyme in the synthesis of prostaglandin D2, an endogenous sleep-promoting neurohormone in the brain. Electromagnetic fields (EMF) in the radio frequency (RF) range have in some studies been associated with disturbed sleep. We studied the concentration of beta-trace protein in blood in relation to emissions from wireless phones. This study included 62 persons aged 18-30 years. The concentration of beta-trace protein decreased with increasing number of years of use of a wireless phone yielding a negative beta coefficient = -0.32, 95% confidence interval -0.60 to -0.04. Also cumulative use in hours gave a negative beta coefficient, although not statistically significant. Of the 62 persons, 40 participated in an experimental study with 30 min exposure to an 890-MHz GSM signal. No statistically significant change of beta-trace protein was found. In a similar study of the remaining 22 participitants with no exposure, beta-trace protein increased significantly over time, probably due to a relaxed situation. EMF emissions may down-regulate the synthesis of beta-trace protein. This mechanism might be involved in sleep disturbances reported in persons exposed to RF fields. The results must be interpreted with caution since use of mobile and cordless phones were self-reported. Awareness of exposure condition in the experimental study may have influenced beta-trace protein concentrations.
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