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- Birringer, M, et al.
(författare)
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Vitamin E analogues as inducers of apoptosis : Structure-function relation
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 88:12, s. 1948-1955
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Tidskriftsartikel (refereegranskat)abstract
- Recent results show that a-tocopheryl succinate (a-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of a-TOS with lower number of methyl substitutions on the aromatic ring were less active than a-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on a-TOS and d-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. a-tocotrienol (a-T3 H) failed to induce apoptosis, while ?-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of ?-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.
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- Lueders, Florian, et al.
(författare)
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Slalom encodes an adenosine 3'-phosphate 5'-phosphosulfate transporter essential for development in Drosophila.
- 2003
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Ingår i: EMBO Journal. - : Wiley. - 1460-2075. ; 22:14, s. 3635-3644
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Tidskriftsartikel (refereegranskat)abstract
- Sulfation of all macromolecules entering the secretory pathway in higher organisms occurs in the Golgi and requires the high-energy sulfate donor adenosine 3'-phosphate 5'-phosphosulfate. Here we report the first molecular identification of a gene that encodes a transmembrane protein required to transport adenosine 3'-phosphate 5'-phosphosulfate from the cytosol into the Golgi lumen. Mutations in this gene, which we call slalom, display defects in Wg and Hh signaling, which are likely due to the lack of sulfation of glycos aminoglycans by the sulfotransferase sulfateless. Analysis of mosaic mutant ovaries shows that sll function is also essential for dorsal–ventral axis determination, suggesting that sll transports the sulfate donor required for sulfotransferase activity of the dorsal–ventral determinant pipe.
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- Maggiore, Salvatore M, et al.
(författare)
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Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury: comparison with the lower inflection point, oxygenation, and compliance
- 2001
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 164:5, s. 795-801
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Tidskriftsartikel (refereegranskat)abstract
- We examined the hypothesis that recording multiple elastic pressure-volume (Pel/V) curves and calculating alveolar derecruitment (V(DER)) induced by decreasing positive end-expiratory pressure (PEEP) may allow determination of alveolar closing pressures, thus helping to select the optimal PEEP level. V(DER) measured in 16 patients with acute lung injury (ALI) was compared with the lower inflection point (LIP) and oxygenation changes. A modified automated method was used to record multiple Pel/V curves at low constant flow. PEEP was decreased in 5-cm H(2)O steps, from 20 or 15 cm H(2)O to 0 cm H(2)O (ZEEP). V(DER) was the volume loss between the curves recorded from PEEP and from ZEEP at the same Pel. Derecruitment occurred at each PEEP decrement, being spread almost uniformly over the 20/15 to 0 cm H(2)O range. V(DER) was not correlated with LIP. V(DER) changes correlated with Pa(O(2))/FI(O(2)) changes (rho = 0.6, p = 0.02). Linear compliance at ZEEP was correlated to V(DER) at PEEP 15 cm H(2)O (rho = 0.9, p = 0.001), suggesting that compliance above LIP may reflect the amount of recruitable lung. Thus, alveolar closure in ALI occurs over a wide range of pressures, and LIP is a poor predictor of alveolar closure.
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