Cholesterol versus cholesterol sulfate: effects on properties of phospholipid bilayers containing docosahexaenoic acid.

The important omega-3 fatty acid docosahexaenoic acid (DHA) is present at high concentration in some membranes that also contain the unusual sterol cholesterol sulfate (CS). The association between these lipids and their effect on membrane structure is presented here. Differential scanning calorimetry (DSC), MC540 fluorescence, erythritol permeability, pressure/area isotherms on lipid monolayers and molecular modeling are used to compare the effect of CS and cholesterol on model phospholipid membranes.

The triggering signal dictates the effect of docosahexaenoic acid on lymphocyte function in vitro.

Docosahexaenoic acid (DHA) is an n-3 fatty acid beneficial to several human conditions including inflammation and autoimmune disease. To better understand the effect of DHA on immunity, we monitored the rise in cytosolic free calcium, interleukin 2 receptor (IL2R) expression, and proliferation of splenic lymphocytes triggered with three different stimuli in the presence or absence of DHA. We found that 10 microg DHA/mL suppressed concanavalin A-induced mitogenesis and the mixed lymphocyte reaction while concurrently enhancing proliferation stimulated with anti-Thy-1 antibodies.

Can docosahexaenoic acid inhibit metastasis by decreasing deformability of the tumor cell plasma membrane?

Murine leukemia cells were fused with small unilamellar vesicles composed of 1-stearoyl, 2-docosahexaenoylphosphatidylcholine. The docosahexaenoic acid (DHA)-modified cells were tested for deformability by forcing them through 5.0-microm Nucleopore filters.

Spleen cell survival and proliferation are differentially altered by docosahexaenoic acid.

Omega-3 fatty acids have diverse health benefits that are not clearly understood. In this study we have examined the effects of the omega-3 fatty acid docosahexaenoic acid (DHA) on mitogen-activated and resting splenic lymphocytes. DHA inhibited lymphocyte proliferation, producing an apparent block or prolongation of S phase, without evidence for direct cytotoxicity.

Function of the conserved Pit-1 gene distal enhancer in progenitor and differentiated pituitary cells.

Pit-1 is a homeodomain transcription factor that is required for the function and survival of the hormone-secreting somatotrope, lactotrope and thyrotrope cells of the anterior pituitary gland. Within the upstream region of the mouse Pit-1 gene at around -10 kb, a complex transcriptional enhancer confers autoregulation and response to hormones and morphogens upon the gene. We demonstrate that this enhancer is conserved in both sequence and function and that related sequences are present in other rodents.

Identification and isoprenylation of plant GTP-binding proteins.

To identify isoprenylated plant GTP-binding proteins, Arabidopsis thaliana and Nicotiana tabacum cDNA expression libraries were screened for cDNA-encoded proteins capable of binding [32P]GTP in vitro. ATGB2, an Arabidopsis homologue of the GTP-binding protein Rab2, was found to bind GTP in vitro and to be a substrate for a geranylgeranyl:protein transferase (GGTase) present in plant extracts. The carboxyl terminus of this protein contains a -GCCG sequence, which has not previously been shown to be recognized by any prenyl:protein transferase (PTase), but which most closely resembles that isoprenylated by the type II GGTase (-XXCC, -XCXC, or -CCXX).

Chemotherapy of pancreatic cancer with the monoterpene perillyl alcohol.

Perillyl alcohol has antitumor activity against rat mammary and liver cancer. Here, we report the chemotherapeutic effects of perillyl alcohol on pancreatic cancer. Perillyl alcohol reduced the growth of hamster pancreatic tumors to less than half that of controls (P < 0.

Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae--a review.

Research on the ergosterol biosynthetic pathway in fungi has focused on the identification of the specific sterol structure required for normal membrane structure and function and for completion of the cell cycle. The pathway and its end product are also the targets for a number of antifungal drugs. Identification of essential steps in ergo-sterol biosynthesis could provide new targets for the development of novel therapeutic agents.

A 42-kilodalton annexin-like protein is associated with plant vacuoles.

A 42-kD, calcium-dependent, membrane-binding protein (VCaB42) was associated with partially purified vacuole membrane. Membrane-dissociation assays indicated that VCaB42 binding to vacuole membranes was selective for calcium over other cations and that 50% of VCaB42 remained membrane bound at 61 +/- 11 nM free calcium. A 13-amino acid sequence obtained from VCaB42 showed 85% similarity with the endonexin fold, a sequence found in the annexin family of proteins that is thought to be essential for calcium and lipid binding.

Growth factor modulation of injury-reactive ependymal cell proliferation and migration.

Injury-reactive ependymal cells from regenerating axolotl spinal cord can be maintained in their mesenchymal outgrowth phase in culture (O'Hara et al., 1992). To address the ability of specific growth factors in stimulating or maintaining migration and proliferation, mesenchymal ependymal cell cultures derived from injured axolotl spinal cord at 2 weeks post-lesioning were used to determine the potential effects of epidermal growth factor, platelet-derived growth factor and transforming growth factor-beta 1.

Cytokinin regulation of a soybean pollen allergen gene.

Cytokinin treatment of suspension-cultured soybean cells stimulated the accumulation of an mRNA, called cim 1, by a factor of ca. 20 within 4 h. Induction of cim 1 mRNA accumulation occurred at benzyladenine concentrations as low as 10(-8) M.

Aged lymphocyte proliferation following incorporation and retention of dietary omega-3 fatty acids.

T cell activation involves events at the plasma membrane; therefore, molecules such as long chain omega-3 fatty acids that alter the structure of the plasma membrane may affect the activation of aged T cells. In this project we investigated whether the incorporation of omega-3 fatty acids (from fish oil), in the presence of vitamin E, improves age-diminished T cell proliferation. Young and old mice were fed diets rich in either fish (menhaden) oil or saturated fat for various lengths of time.

Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans.

The identification of the precise structural features of yeast sterol molecules required for the essential "sparking" function has been a controversial area of research. Recent cloning and gene disruption studies in Saccharomyces cerevisiae have shown that C-24 methylation (ERG6), C-5 desaturation (ERG3) and delta 8-delta 7 isomerization (ERG2) are not required, while C-14 demethylation (ERG11) and C-14 reduction (ERG24) are each required for aerobic viability. Earlier observations had indicated that C-14 demethylase deficient strains could be restored to aerobic growth by suppressor mutations that caused a deficiency in C-5 desaturase.

Molecular modeling: a tool for predicting anthelmintic activity in vivo.

The structural and electronic features of the broad-spectrum benzimidazole anthelmintic mebendazole [MBZ, methyl 5-(benzoyl)-benzimidazole-2-carbamate] have been determined using a combination of quantum mechanics, molecular graphics, and molecular modeling techniques. Using conformational analyses and quantum mechanics, we found that the three-dimensional structure and electronic features of MBZ were consistent with those previously reported for highly active broad-spectrum benzimidazole anthelmintics and that in vivo drug efficacy against Hymenolepis diminuta depends upon the orientation of the benzoyl group at position 5 on the heterocyclic ring system, the magnitude of the molecular dipole moment, and the percentage of polar surface area. The chemotherapeutic actions of MBZ on H.