A convenient synthesis for enantiomeric pure 1-O-(1'-O-alkyl-sn-glycero-3'-phospho)-D (or L)-myo-inositol, 1-O-(1'-O-acyl-sn-glycero-3'-phospho)-D (or L)-myo-inositol and alkylphospho-1-D (or L)-myo-inositol has been described. Starting from myo-inositol, penta-O-acetyl-myo-inositol was made in five steps. Then enantiomeric purification was done by a diastereomeric salts separation method, and the purity of each enantiomer was spectroscopically measured (19F-NMR). The phosphodiester was made via phosphoramidites. The enantiomeric products (greater than 99% optical purity) of all compounds were easily obtained in large quantities (5-10 g). Synthetic phosphatidylinositol analogues of precisely defined structure and configuration are interesting tools for studying signal transduction mechanism and cell activity modulation.

Lysophospholipids↗

PubMedDate not supplied

A new approach for chemotherapy against Entamoeba histolytica.

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Amebicides↗

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Interaction of streptolysin-O with natural and artificial membranes.

1. Kinetic studies on the binding of 125I-streptolysin-O exhibited immediate fixation of activation toxin to natural and artificial membranes. Once fixed to the membrane no release of Streptolysin-O or Streptolysin-O-lipid-complexes has been observed. 2. In contrast to activated toxin (free SH-groups!), oxidized Streptolysin-O was shown to become also fixed to membranes, however, with different binding kinetics. The binding of oxidized amterial was clearly dependent on temperature and time. When the toxin was oxidized twice the amount of labelled material was bound as compared with the hemolytically active Streptolysin-O. This suggests that oxidized Streptolysin-O, too, possesses a "binding site" within the molecule, though free SH-groups were expected to be essential for toxin fixation at the membrane. It has been shown that oxidized (inactive) and reduced (active) Streptolysin-O forms stable "complexes" with liposomes in aqueous which could be separated by chromatography on Sepharose gels. 3. The binding of 125I-toxin to membranes and liposomes was specific since specific antisera against Streptolysin-O inhibited fixation of toxin completely. 4. Hydrolysis of phospholipids and release of lysophosphatides by Streptolysin O esterase (EC 2.1.2.2) has not been observed, thus providing no evidence for an enzymatic concept for membrane damage.

Antigen-Antibody Reactions↗

PubMedDate not supplied

Erucylphosphocholine-induced apoptosis in chemoresistant glioblastoma cell lines: involvement of caspase activation and mitochondrial alterations.

Intrinsic chemoresistance constitutes a major problem in the therapy of malignant gliomas. In vitro experiments with four astrocytoma/glioblastoma (AC/GBM) cell lines revealed that the chemoresistance of two cell lines, A172 and T98G, to cisplatin and etoposide was due to resistance to drug-induced apoptosis. In contrast, all the AC/GBM cell lines tested were sensitive to treatment with the lipophilic ether lipid erucylphosphocholine, ErPC. ErPC-induced apoptosis was independent of wild-type p53-signaling and triggering of the CD95/CD95 ligand (CD95L) system. Inhibition of protein and RNA synthesis by cycloheximide and actinomycin D did not abrogate ErPC-induced apoptosis. However, expression of members of the bcl-2 protein family was modulated during ErPC treatment. Activation of caspase 3 and mitochondrial alterations were central to ErPC-induced apoptosis. We conclude that ErPC-induced activation of the mitochondrial pathway enables cell death in the chemoresistant AC/GBM cells.

Animals↗

PubMedDate not supplied

Hexadecylphosphocholine: determination of serum concentrations in rats.

A sensitive and quantitative determination of the concentration of hexadecylphosphocholine in serum is described. After HPLC separation, the concentration of hexadecylphosphocholine is determined by phosphate analysis. According to this method, the half-life of hexadecylphosphocholine in serum rats is about 96 h. A steady-state serum concentration of 110 microM is reached after 2 weeks of daily treatment with 10 mg/kg hexadecylphosphocholine. The described method has general application for other compounds with similar structures. For instance, serum levels of alkyllysophosphocholines such as 1-0-octadecyl-2-0-methyl- racglycero-3-phosphocholine can be determined using this method.

Animals↗

PubMedDate not supplied

Antitumor effects of erucylphosphocholine on brain tumor cells in vitro and in vivo.

The antineoplastic activity of erucylphosphocholine (ErPC) on C6 rat glioma cells and the human glioblastoma cell lines A172 and T98G was studied in vitro. ErPC exerted concentration- and time-dependent cytostatic and cytotoxic actions. The effects of ErPC on C6 cells were stronger than hexadecylphosphocholine and similar to 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine. The human cell lines were more sensitive to ErPC (LC50 = 36 microM and 29 microM) than C6 cells (LC50 = 70 microM) (48 hours, WST-1-test). Morphological characteristics of apoptotic cell death were observed. Rats bearing intracerebral and subcutaneous gliomas were treated with intravenous ErPC for 30 days to determine the antitumor effects of ErPC in vivo. ErPC accumulation in subcutaneous tumors was higher than in brain tissue. Peripheral tumors revealed a better response than CNS-tumors. There was a strong negative relationship between the concentration of ErPC and the weight of peripheral tumors. ErPC is considered to be promising for chemotherapy of malignant brain tumors.

Animals↗