Biofactors - Volume 10, issue 2-3

Article Type: Other

Citation: Biofactors, vol. 10, no. 2-3, pp. 83-83, 1999

Authors: Swindell, Eric C. | Eichele, Gregor

Article Type: Research Article

Citation: Biofactors, vol. 10, no. 2-3, pp. 85-89, 1999

Authors: Carlberg, Carsten

Article Type: Research Article

Abstract: Vitamin A (retinol) and vitamin D are lipid soluble vitamins that are precursors of the nuclear hormones all‐trans retinoic acid (RA) and 1\alpha ,25‐dihydroxyvitamin D_{3} (VD) that bind with high affinity to their cognate nuclear receptors, referred to as retinoic acid receptor (RAR) and vitamin D receptor (VDR). Both types of nuclear receptors are structurally related and belong to the same subclass of the nuclear receptor superfamily, a large family of ligand‐inducible transcription factors. Both RAR and VDR form heterodimers preferentially with the nuclear receptor for 9‐cis RA, referred to as the retinoid X receptor (RXR), but …functional RAR‐VDR heterodimers have also been observed. Moreover, both types of nuclear receptors interact in a ligand‐dependent fashion with members of the same class of co‐activator, co‐repressor and co‐integrator proteins. These similar molecular mechanisms of action provide several possibilities for an interaction of RARs with VDR that are all based on allosteric protein–protein interactions. These interactions can result in either an additive or a transrepressive functional interference between RA and VD. The two remaining lipid soluble vitamins, vitamins E and K, are not known to interact with nuclear receptors, but their structure does not exclude this possibility. Moreover, for vitamin E modulatory effects on transcription factors, such as AP‐1, have been described. This review will discuss briefly gene regulation by the four lipid soluble vitamins. Show more

Keywords: Vitamins A, D, E and K, nuclear receptors, transcriptional regulation

Citation: Biofactors, vol. 10, no. 2-3, pp. 91-97, 1999

Authors: Vershinin, Alexander

Article Type: Research Article

Abstract: Carotenoids first emerged in archaebacteria as lipids reinforcing cell membranes. To serve this function their long molecules have extremely rigid backbone due to the linear chain of usually 10 to 11 conjugated C= C bonds in trans‐configuration – the length corresponding the thickness of hydrophobic zone of membrane which they penetrate as “molecular rivets”. Carotenoids retain their membrane‐reinforcing function in some fungi and animals. The general structure of carotenoid molecule, originally having evolved for mechanical functions in membranes, possess a number of other properties that were later used for independent functions. The most striking fact is that these …properties proved to fit some new functions to perfection. – The polyene chain of 9–11 double bonds absorbs light precisely in the gap of chlorophyll absorption – function as accessory light‐harvesting pigments in all plants; – Unique arrangement of electronic levels owing to the by polyene chain structure makes carotenoids the only natural compounds capable of excitation energy transfer both (i) from carotenoid excited state to chlorophyll in the light‐harvesting complex and (ii) from triplet chlorophyll or singlet oxygen to carotenoid in photosynthetic reaction centers – protection of RC from photodamage. The linear system of conjugated C= C bonds provides high reducing potential of carotenoid molecules making them potent antioxidants in lipid formations. Still, there is a lack of evidence of the chemical antioxidant function of carotenoids, especially in higher organisms; most data demonstrate an antioxidant ability rather than a function. Carotenoids have many other independent biological functions, including: specific coloration patterns in plants and animals, screening from excessive light and spectral filtering, defense of egg proteins from proteases in some invertebrates; the direct carotenoid derivative – retinal – acts as visual pigment in all animals and as chromophore in bacteriorhodopsin photosynthesis, retinoic acid in animals and abscisic acid in plants serve as hormones. All these functions utilize various properties (mechanical, electronic, stereospecific) of a single structure evolved in bacteria for a single membrane‐reinforcing function, thus demonstrating an example of pure evolutionary preadaptation. One of the practical conclusions that can be reached by reviewing uniquely diverse properties and functions of carotenoids is that, when considering possible mechanisms of their effects in organisms (e.g., anticarcinogenic action), all their functional traits should be taken into account. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 99-104, 1999

Authors: Siems, Werner G. | Sommerburg, Olaf | van Kuijk, Frederik J.G.M.

Article Type: Research Article

Abstract: Major carotenoids of human plasma and tissues were exposed to radical‐initiated autoxidation conditions. The consumption of lutein and zeaxanthin, the only carotenoids in the retina, and lycopene and \beta ‐carotene, the most effective quenchers of singlet oxygen in plasma, were compared. Under all conditions of free radical‐initiated autoxidation of carotenoids which were investigated, the breakdown of lycopene and \beta ‐carotene was much faster than that of lutein and zeaxanthin. Under the influence of UV light in presence of Rose Bengal, by far the highest breakdown rate was found for \beta ‐carotene, followed by lycopene. Bleaching of …carotenoid mixtures mediated by NaOCl, addition of azo‐bis‐isobutyronitril (AIBN), and the photoirradiation of carotenoid mixtures by natural sunlight lead to the following sequence of breakdown rates: lycopene > \beta ‐carotene > zeaxanthin > lutein. The slow degradation of the xanthophylls zeaxanthin and lutein may be suggested to explain the majority of zeaxanthin and lutein in the retina of man and other species. In correspondence to that, the rapid degradation of \beta ‐carotene and lycopene under the influence of natural sunlight and UV light is postulated to be the reason for the almost lack of those two carotenoids in the human retina. Nevertheless, a final proof of that theory is lacking. Show more

Keywords: Carotenoids, lutein, zeaxanthin, lycopene, \beta‐carotene, retina, UV light, photoirradiation

Citation: Biofactors, vol. 10, no. 2-3, pp. 105-113, 1999

Authors: Traber, Maret G.

Article Type: Research Article

Citation: Biofactors, vol. 10, no. 2-3, pp. 115-120, 1999

Authors: Sommerburg, O. | Sostmann, K. | Grune, T. | Ehrich, J.H.H.

Article Type: Research Article

Abstract: Background: MDA, a major product of LPO, was shown to be increased in plasma of patients with end‐stage renal failure (ESRF) undergoing hemodialysis (HD). Elevated oxidative stress in ESRF patients is a result of multiple pathogenetic factors. HD treatment has been shown to be one important cause of accelerated radical generation. The aim of our study was to examine whether treatment with a dialysis membrane which has alpha‐tocopherol hydrophobically bonded to its surface (Excebrane by Terumo, Japan) can decrease oxidative stress due to HD. Methods: 10 ESRF patients undergoing HD three times weekly were examined. First, analysis was done …when patients were still dialysed with the membranes used before the study. Thereafter, samples were taken when patients were dialysed first time with the Excebrane membrane, and six weeks after Excebrane treatment. Samples were collected always before and after HD session. A method with HPLC‐separation and flourimetric detection was used to measure plasma concentration of MDA. Results: After HD with the regularly used membranes MDA was found significantly increased (before HD 1.92 [1.81–2.02] \mu M (median and interquartile ranges) vs. after HD 2.26 [2.02–2.60] \mu M, p<{} 0.05) suggesting that MDA was produced during HD. The first time Excebrane was used MDA was decreased significantly (before HD 2.04 [1.95–2.88] \mu M vs. after HD 1.35 [1.19–1.92] \mu M, p<{} 0.05). After six weeks of Excebrane treatment, plasma MDA did not change significantly during HD (before HD 2.01 [1.69–2.62] \mu M vs. after HD 1.95 [1.42–2.20] \mu M). Conclusion: Oxidative stress due to HD might be significantly decreased by the Excebrane membrane. However, after six weeks of treatment with Excebrane no effect was seen on the initial plasma concentration of MDA compared to the time before. Show more

Keywords: Hemodialysis, vitamin E, end‐stage renal failure, antioxidants, radicals, oxidative stress

Citation: Biofactors, vol. 10, no. 2-3, pp. 121-124, 1999

Authors: Lotito, Silvina B. | Fraga, César G.

Article Type: Research Article

Abstract: We evaluated the antioxidant effect of (+ )‐catechin (CTCH), in the presence of physiological antioxidant levels of ascorbic acid (AA), \alpha ‐tocopherol (AT) and beta‐carotene (BC), in human plasma oxidised with AAPH. Following a five‐hour incubation, the formation of lipid oxidation products (TBARS) was almost doubled, and the concentrations of lipid soluble antioxidants were 10 to 30% from the initial levels. In these conditions, AA was consumed within the first hour of incubation. The addition of CTCH prevented AT and BC depletion and TBARS formation, but had no effect on AA consumption. When the kinetics of oxidation were …analysed CTCH oxidation preceded lipid soluble antioxidant depletion, but no consumption of CTCH was associated to AA oxidation. Considering that CTCH could contribute to the antioxidant activity of red wine, we first characterised both the antioxidant capacity and CTCH content of several wines. The wines with highest content of CTCH and antioxidant activity were also the most effective in preventing AAPH‐mediated oxidation of plasma vitamin E. Results support the idea that CTCH could have a role as a physiological antioxidant in human plasma, and that CTCH of wine could contribute to the antioxidant status of human plasma. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 125-130, 1999

Authors: Kishi, Takeo | Takahashi, Takayuki | Usui, Akinori | Okamoto, Tadashi

Article Type: Research Article

Abstract: Ubiquinone (UQ) reductase responsible for reduction of non‐mitochondrial UQ was investigated in rats toward demonstrating an antioxidant role of UQ. In the liver, most of cellular UQ‐10 reductase activity was attributable to a novel NADPH‐UQ reductase in cytosol. The enzyme was not inhibited by dicumarol and rotenone, and had a K_\mathrm{m} of 19 \mu M for NADPH and 307 \mu M for NADH at the optimum pH 7.4. The enzyme was purified 300‐fold to apparent homogeneity from the liver cytosol by an affinity chromatographic method. The purified enzyme reduced UQ‐10 in lecithin liposomes, and protected the …liposomes from lipid peroxidation. Furthermore, supplementation of rats with UQ‐10 was observed to increase the enzyme level in their livers without affecting levels of other antioxidant factors. The observations suggested that cytosolic NADPH‐UQ reductase is responsible for cellular UQ redox cycle as an endogenous antioxidant. Show more

Keywords: Ubiquinone, quinone reductases, NADPH dehydrogenases, antioxidants, rats

Citation: Biofactors, vol. 10, no. 2-3, pp. 131-138, 1999

Authors: Sakamoto, Wataru | Nishihira, Jun | Fujie, Katsutoshi | Iizuka, Tadashi | Handa, Hiroshi | Ozaki, Mitsuru | Yukawa, Susumu

Article Type: Research Article

Abstract: Macrophage migration inhibitory factor (MIF), a putative cytokine involved in inflammatory and immune responses, was identified in rat peritoneal macrophages by Western blot analysis and its secretion into culture medium by enzyme‐linked immunosorbent assay. To clarify the possibility of vitamin E as an immune modulator, we investigated the effect of vitamin E on MIF production in macrophages in response to calcium ionophore A23187 and lipopolysaccharide (LPS). Intraperitoneal injections of vitamin E (5 mg per rat) for 6 successive days resulted in a significant increase of \alpha ‐tocopherol content in peritoneal macrophages. \alpha ‐Tocopherol content of macrophages in vitamin …E‐treated rats was 478.3 \pm 90.7 ng/10^{6} cells, whereas in control rats it was 1.5 \pm 0.5 ng/10^{6} cells. For the control macrophages, total MIF content of the medium (2.5 \times 10^{6} cells/18 ml) without stimulation was 40.7 \pm 3.6 ng after 14 h culture, whereas stimulation with calcium ionophore A23187 (400 nM) and LPS (5.0 \mu g/ml) induced the elevation of MIF content to 65.9 \pm 7.5 ng and 74.3 \pm 10.4 ng, respectively (p<{} 0.05, n={} 3). On the other hand, vitamin E‐enriched macrophages without stimulation showed less MIF content (14.0 \pm 4.2 ng) than the control (p<{} 0.05, n={} 3). Similarly, the increase of MIF of vitamin E‐treated macrophages was significantly suppressed after stimulation with calcium ionophore A23187 or LPS, compared with the control macrophages (p<{} 0.01, n={} 3). From analysis of intracellular MIF content by Western blot, we found no alteration of intracellular MIF content of vitamin E‐macrophages, in contrast to the decreased content of control stimulated‐macrophages, showing that vitamin E suppressed MIF secretion into the culture medium. Taken together, these results indicate that vitamin E may contribute to the regulation of inflammatory and immune responses through regulation of MIF secretion, possibly by modulating macrophage‐membrane architecture. Show more

Keywords: Vitamin E, macrophages, macrophage migration inhibitory factor (MIF), lipopolysaccharide (LPS), calcium ionophore A23187

Citation: Biofactors, vol. 10, no. 2-3, pp. 139-143, 1999