melitten and Lymphoma

D-Pro14 melittin was synthesized to investigate the effect of increasing the angle of the bend in the hinge region between the helical segments of the molecule. Structural analysis by nuclear magnetic resonance indicated that, in methanol, the molecule consisted of two helices separated at Pro14, as in melittin. However, the two helices in D-Pro14 melittin were laterally displaced relative to each other by approximately 7 A, and in addition, there was a small rotation of the carboxyl-terminal helix relative to the amino-terminal helix around the long axis of the molecule. The peptide had less than 5% of the cytolytic activity of melittin. Modification of Arg22 with the 2,2,5,7,8-pentamethyl-chroman-6-sulphonyl (pmc) group restored hemolytic activity to close to that of unmodified melittin. Replacement of Arg22 with Phe was less effective in restoring hemolytic activity. Electron-paramagnetic resonance studies suggest that there is a positive correlation between hemolytic activity of the peptides and interaction with phospholipid bilayers.

Topics: Cell Death; Erythrocytes; Hemolysis; Humans; Lipids; Lymphoma; Melitten; Methanol; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Secondary; Structure-Activity Relationship

Cyclosporin A, immunosuppressive agent, reversibly blocks the mitogenic effect of prolactin in rat lymphoma Nb-2 cells and removal from the medium leads to a rapid and transient induction of c-fos mRNA. Activators of protein kinase C, such as TPA, mellitin and phospholipase C and the calcium ionophore, A23187, induced c-fos mRNA in the presence or absence of cyclosporin A. Activators of the cAMP pathway such as forskolin, dBcAMP and cholera toxin failed to induce c-fos mRNA in the presence or absence of cyclosporin A. These results suggest that cyclosporin A may act at the level of protein kinase C.

Topics: Animals; Calcimycin; Cyclosporins; Enzyme Activation; Gene Expression; Lymphoma; Melitten; Protein Kinase C; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fos; Rats; RNA, Messenger; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Type C Phospholipases

12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent tumour promoter, was tested for its effects on the proliferation of the human Burkitt lymphoma cell line, Namalwa, and the synthesis of interferon by these cells. At nanomolar concentrations, TPA blocked thymidine incorporation into cellular DNA by more than 90% within 24 h. TPA-treated cells produced about 20-fold more interferon in response to Sendai virus than did untreated controls and simultaneous treatment with TPA and sodium n-butyrate gave a further two- to three-fold enhancement. Neither of these effects of TPA was reversed on removal of the compound; furthermore, exposure of Namalwa cells to TPA for only 1 h was sufficient for full activity. 4-O-methyl-TPA, a compound only marginally active as a tumour promoter, showed effects similar to TPA, but only at concentrations 300-fold higher. In contrast to its effects on Namalwa cells, TPA did not affect synthesis of interferon in response to Sendai virus in two other Burkitt lymphoma lines (Raji and Daudi) nor in the Epstein-Barr virus (EBV)-negative lymphoma line, BJAB; it inhibited interferon production in the human myeloid cell line, HL-60.

Topics: Burkitt Lymphoma; Butyrates; Cell Line; DNA; Humans; Interferons; Lymphoma; Melitten; Parainfluenza Virus 1, Human; Phorbols; Tetradecanoylphorbol Acetate; Tretinoin