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  • 1.
    Bentinger, Magnus
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet.
    Kania, Magdalena
    Danikiewicz, Witold
    Kaczorowska, Ewa
    Wojcik, Jacek
    Brismar, Kerstin
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet.
    Chojnacki, Tadeusz
    Swiezewska, Ewa
    Tekle, Michael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet.
    Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis2014In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1841, no 7, p. 977-986Article in journal (Refereed)
    Abstract [en]

    2,3-Oxidosqualene is an intermediate in cholesterol biosynthesis and 2,3:22,23-dioxidosqualene act as the substrate for an alternative pathway that produces 24(S),25-epoxycholesterol which effects cholesterol homeostasis. In light of our previous findings concerning the biological effects of certain epoxidated all-trans-polyisoprenes, the effects of squalene carrying epoxy moieties on the second and third isoprene residues were investigated here. In cultures of HepG2 cells both monoepoxides of squalene and one of their hydrolytic products inhibited cholesterol synthesis and stimulated the synthesis of coenzyme Q (CoQ). Upon prolonged treatment the cholesterol content of these cells and its labeling with [H-3]mevalonate were reduced, while the amount and labeling of CoQ increased. Injection of the squalene monoepoxides into mice once daily for 6 days elevated the level of CoQ in their blood, but did not change the cholesterol level. The same effects were observed upon treatment of apoE-deficient mice and diabetic GK-rats. This treatment increased the hepatic level of CoQ10 in mice, but the amount of CoQ9, which is the major form, was unaffected. The presence of the active compounds in the blood was supported by the finding that cholesterol synthesis in the white blood cells was inhibited. Since the ratio of CoQ9/CoQ10 varies depending on the experimental conditions, the cells were titrated with substrate and inhibitors, leading to the conclusion that the intracellular isopentenyl-PP pool is a regulator of this ratio. Our present findings indicate that oxidosqualenes may be useful for stimulating both the synthesis and level of CoQ both in vitro and in vivo.

  • 2.
    Bentinger, Magnus
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Tekle, Michael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Coenzyme Q - Biosynthesis and functions2010In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 396, no 1, p. 74-79Article in journal (Refereed)
    Abstract [en]

    In addition to its role as a component of the mitochondrial respiratory chain and our only lipid-soluble antioxidant synthesized endogenously, in recent years coenzyme Q (CoQ) has been found to have an increasing number of other important functions required for normal metabolic processes. A number of genetic mutations that reduce CoQ biosynthesis are associated with serious functional disturbances that can be eliminated by dietary administration of this lipid, making CoQ deficiencies the only mitochondrial diseases which can be successfully treated at present. In connection with certain other diseases associated with excessive oxidative stress, the level of CoQ is elevated as a protective response. Aging, certain experimental conditions and several human diseases reduce this level, resulting in serious metabolic disturbances. Since dietary uptake of this lipid is limited, up-regulation of its biosynthetic pathway is of considerable clinical interest. One approach for this purpose is administration of epoxidated all-trans polyisoprenoids, which enhance both CoQ biosynthesis and levels in experimental systems.

  • 3.
    Bentinger, Magnus
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet, Sweden.
    Tekle, Michael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet, Sweden.
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet, Sweden.
    Brismar, Kerstin
    Gustafsson, Jan-Åke
    Steffensen, Knut R.
    Sergiu-Bogdan, Catrina
    Influence of liver-X-receptor on tissue cholesterol, coenzyme Q and dolichol content2012In: Molecular membrane biology, ISSN 0968-7688, E-ISSN 1464-5203, Vol. 29, no 7, p. 299-308Article in journal (Refereed)
    Abstract [en]

    The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) alpha, beta and double knockout mice. An extensive or moderate increase of total cholesterol in the double KO mice was found in all organs elicited by the increase of the esterified form. In LXR alpha and double KO mice, coenzyme Q (CoQ) was decreased in liver and increased in spleen, thymus and lung, while dolichol was increased in all organs investigated. This effect was confirmed using LXR-agonist GW 3965. Analysis of CoQ distribution in organelles showed that the modifications are present in all cellular compartments and that the increase of the lipid in mitochondria was the result of a net increase of CoQ without changing the number of mitochondria. It appears that LXR influences not only cellular cholesterol homeostasis but also the metabolism of CoQ and dolichol, in an indirect manner.

  • 4.
    Dallner, G.
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Stocker, R.
    Coenzyme Q2010In: Encyclopedia of Dietary Supplements / [ed] P.M. Coates, New York: Informa Healthcare , 2010, p. 157-165Chapter in book (Other academic)
  • 5.
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Regulation of coenzyme Q biosynthesis2011In: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 164, p. s12-S12Article in journal (Other academic)
  • 6. Surmacz, Liliana
    et al.
    Wojcik, Jacek
    Kania, Magdalena
    Bentinger, Magnus
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danikiewicz, Witold
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Surowiecki, Przemyslaw
    Cmoch, Piotr
    Swiezewska, Ewa
    Short-chain polyisoprenoids in the yeast Saccharomyces cerevisiae - New companions of the old guys2015In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1851, no 10, p. 1296-1303Article in journal (Refereed)
    Abstract [en]

    Dolichols are, among others, obligatory cofactors of protein glycosylation in eukaryotic cells. It is well known that yeast cells accumulate a family of dolichols with Dol-15/16 dominating while upon certain physiological conditions a second family with Dol-21 dominating is noted. In this report we identified the presence of additional short-chain length polyprenols - all-trans Pren-7 in three yeast strains (SS328, BY4741 and L5366), Pren-7 was accompanied by traces of putative Pren-6 and -8. Moreover, in two of these strains a single polyprenol mainly-cis-Pren-11 was synthesized at the stationary phase of growth. Identity of polyprenols was confirmed by HR-HPLC/MS, NMR and metabolic labeling. Additionally, simvastatin inhibited their biosynthesis.

  • 7.
    Tekle, Michael
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gromadzinska, Jolanta
    Joksic, Gordana
    Antic, Ruza
    Nilsson, Robert
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Undén, Anna-Lena
    Brismar, Kerstin
    Plasma levels of insulin-like growth factor-I, insulin-like growth factor binding protein-1, coenzyme Q10 and vitamin E in female populations from Poland, Serbia and Sweden2010In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 36, no 2, p. 188-194Article in journal (Refereed)
    Abstract [en]

    Exposure to environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs), life style and nutritional status of a population are important factors that may influence normal serum levels of antioxidants and the insulin-like growth factor system. In this study we examined serum levels of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), coenzyme Q10 (CoQ) and vitamin E in healthy female populations (n = 4 x 100) aged 19-59 years from Poland (PL), Sweden (SE), Serbia I (SR I) and Serbia II (SR II). The last group lived in an environmental emergency area affected by the bombings of 1999 in Serbia. The Polish and SR I cohorts exhibited low IGFSD-score levels, (-2 to +/-0), compared to females from SE with IGFSD-score 0. In the SIR II population, the IGFSD range was between -1 and 1. The IGFBP-1 levels of the Polish and SIR I groups were lower than in the Swedish population, while the SR II levels showed a broader distribution, 20-80 mu g/l. The CoQ values in the Swedish and Polish samples were around 1 nmol/ml. In contrast. the SIR I cohorts exhibited higher concentrations, 1.5-3.5 nmol/ml and the SIR II group had extremely low levels, <0.5 nmol/ml. The vitamin E concentrations were similar in the Polish and Swedish populations, 20-40 nmol/ml, while it was twice as high, 40-80 nmol/ml in the SR I and very low in the SIR II group, which is half of the Polish and Swedish cohorts. These results suggest that different lifestyles and environmental factors affect both the IGF system and the antioxidants CoQ10 and vitamin E in female populations in Europe. The females living in the polluted area had different patterns of both the IGF and antioxidant systems. These findings may explain differences in morbidity and mortality in these countries.

  • 8. Theuri, G.
    et al.
    Dallner, Gustav
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Brismar, K.
    Tekle, Michael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Effects of lifestyle on plasma levels of the IGF system and the antioxidants coenzyme Q10 and vitamin E in Kenyan rural and urban populations2013In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 23, no 3, p. 68-75Article in journal (Refereed)
    Abstract [en]

    Objective: Overnight fasting blood plasma insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), coenzyme Q10, (CoQ) vitamin E and plasma lipids were compared between a semi-nomadic Samburu population and relatively urbanized cohorts from Nairobi, Kenya. Research design and methods: 143 middle aged subjects without known diabetes were included. IGF-I and IGFBP-1 were analyzed by RIA, and CoQ and vitamin E by HPLC. Plasma lipid levels were analyzed by standard laboratory methods routinely used in the clinics. Results: The age adjusted IGF-I serum levels were low in the Samburu male and female populations, ranging from 0 to -4 IGFSD-score (SDS), and a minor part of the investigated population reaching as low as -5 and -7 SDS. The Nairobi cohorts showed significantly higher values reaching from -2.5 to + 1 SDS (P<0.0001). The nomadic Samburu population showed fasting IGFBP-1 values ranging from 30-100 mu g/l, while that of the urbanized Nairobi cohorts was considerably lower (25-60 mu g/l) (P<0.0001). CoQ concentrations of the Nairobi cohorts were 1.5-2.0 nmol/ml similar to the levels found in several European countries. The Samburu population on the other hand showed extremely high CoQ values ranging from 2 to 9 nmol/ml (P<0.0001). Vitamin E levels of the Nairobi group were low (5-20 nmol/ml), but the Samburu population had even lower levels ranging from 3 to 15 nmol/ml (P<0.0001). Plasma lipid levels such as cholesterol, triglycerides, LDL/HDL, ApoB/ApoA ratios as well as BMI and weight were significantly higher in the Nairobi population (P<0.0001). Conclusions: Low IGF-I and high IGFBP-1 levels of the Samburu cohorts indicate malnutrition. High lipid levels of the Nairobi cohorts indicate that these groups have several risk factors for cardiovascular diseases and diabetes type2.

1 - 8 of 8
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