Search results for "synthesis"

Selective permeabilization of infected host cells with pore-forming proteins provides a novel tool to study protein synthesis and viability of the in…

2001

Mitogenic effects of phospholipase D and phosphatidic acid in transiently permeabilized astrocytes: effects of ethanol.

2003

Investigations of lipid-mediated signalling pathways are often limited by a lack of methods for the intracellular delivery of lipid messengers. We established a procedure for the transient permeabilization of astrocytes by an oxygen-insensitive mutant of streptolysin-O (SLO) to investigate the participation of the phospholipase D (PLD) signalling pathway in astroglial cell proliferation. Exogenous PLD, when incubated in the presence of SLO, caused an increase in DNA synthesis (measured by thymidine incorporation) which was completely suppressed by ethanol (0.3%, v/v). In parallel experiments, phosphatidic acid also induced a dose-dependent mitogenic response which, however, was not affected…

Yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for the rapid reprogramming of translation after hyperosmotic shock.

2011

Global translation is inhibited in Saccharomyces cerevisiae cells under osmotic stress; nonetheless, osmostress-protective proteins are synthesized. We found that translation mediated by the mRNA cap-binding protein Cbc1 is stress-resistant and necessary for the rapid translation of osmostress-protective proteins under osmotic stress.

Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells.

2010

Background Cancer cells present a sustained de novo fatty acid synthesis with an increase of saturated and monounsaturated fatty acid (MUFA) production. This change in fatty acid metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (Scd1), which catalyses the transformation of saturated fatty acids into monounsaturated fatty acids (e.g., oleic acid). Several reports demonstrated that inhibition of Scd1 led to the blocking of proliferation and induction of apoptosis in cancer cells. Nevertheless, mechanisms of cell death activation remain to be better understood. Principal Findings In this study, we demonstrated that Scd1 extinction by siRNA triggered abolition of de nov…

Novel [1,2,3]triazolo[1,5-a]pyridine derivatives are trypanocidal by sterol biosynthesis pathway alteration.

2019

Aim: To study a new series of [1,2,3]triazolo[1,5-α]pyridine derivatives as trypanocidal agents because current antichagasic pharmacologic therapy is only partially effective. Materials & methods: The effect of the series upon Trypanosoma cruzi epimastigotes and murine macrophages viability, cell cycle, cell death and on the metabolites of the sterol biosynthesis pathway was measured; also, docking in 14α-demethylase was analyzed. Results: Compound 16 inhibits 14α-demethylase producing an imbalance in the cholesterol/ergosterol synthesis pathway, as suggested by a metabolic control and theoretical docking analysis. Consequently, it prevented cell proliferation, stopping the cellular cy…

Solid-Phase Synthesis and Biological Evaluation of a Teleocidin Library—Discovery of a Selective PKC Down Regulator

2000

Protein kinaseC (PKC) is linked to the signal-induced modulation of a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis, and tumor development. The design and synthesis of small molecules that regulate these different cellular signaling systems is at the forefront of modern drug design. Herein we report a) an efficient method for the synthesis of indolactamV (6), a PKC activator, and its N13-des(methyl) analogues (19) using a regioselective organometallic transformation, a convenient aminomalonate derivative (10) to introduce the appropriate functionality and an enantiospecific enzymic hydrolysis as key steps; b) the use of this method in the first so…

Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. De…

1987

Two pyridinedicarboxylates, predicted [Hanauske-Abel (1983) M.D.-Ph.D. Thesis, Philipps Universität Marburg] and later found to be potent reversible inhibitors of purified prolyl 4-hydroxylase [Majaama, Hanauske-Abel, Günzler & Kivirikko (1984) Eur. J. Biochem. 138, 239-245] were investigated with respect to their effect on hydroxyprolyl biosynthesis in the fibroblast/collagen and the macrophage/Clq systems, and the effect was compared with that of the iron chelator 2,2′-dipyridyl, the compound usually employed to inhibit cellular hydroxyprolyl formation. Only the enzyme-mechanism-derived pyridinedicarboxylates were highly selective inhibitors, and only they lacked overt cytotoxicity. M…

Expression of protein kinase C gene family members is temporally and spatially regulated during neural development in vitro.

1998

We used primary cultures of rat hippocampal neurons and PCC7-Mz1 cells to correlate the expression of the protein kinase C (PKC) gene family with specific events during neural differentiation. Multipotent PCC7-Mz1 embryonic carcinoma stem cells develop into a tissue-like pattern of neuronal, fibroblast-like and astroglial cells by all-trans retinoic acid (RA) treatment. Western blot analyses demonstrate that PKCalpha, betaI, gamma, theta, mu, lambda, and zeta were constitutively expressed but the expression of PKCbetaII, delta, epsilon, and eta was up-regulated three days after addition of RA when cells mature morphologically. While the protein levels of the PKC isoforms betaII, delta and e…

Synthesis and Antitumor Properties of 2,5-Bis(3'-indolyl) thiophenes: Analogues of Marine Alkaloid Nortopsentin

2007

A series of 11 bis-indolylthiophenes of formula I were obtained by cyclization of bis-indole 1,4-diketones using Lawesson''s reagent. Derivs. I (R = OMe, R1 = SO2Ph), I (R = OMe, R1 = Me), I (R = Cl, R1 = Me), and I (R = OMe, R1 = H) were selected to be evaluated in the full panel of about 60 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity generally in the micromolar range. The most sensitive cell lines were: CCRF-CEM, MOLT-4, HL60 (TB), and RPMI-8226 of the leukemia subpanel, HT29 and HCC-2998 cell lines of the colon sub-panel, NCI-H522 of the non-small cell lung cancer sub-panel, LOX IMVI of the melanoma sub-panel, and UO-31 of the re…

Spontaneous lymphokine synthesis by human blood mononuclear cells

1975

LYMPHOCYTES, after antigenic stimulation, may synthesise and release biologically active soluble factors other than antibodies. These mediators were termed lymphokines by Dumonde1, and the most extensively studied and best characterised are migration inhibitory factors which can inhibit the migration of macrophages or leukocytes: this is the property used for their in vitro bioassay. Apart from antigens, various other stimuli may trigger lymphokine synthesis by lymphocytes, for example, polyclonal mitogens2, anti-immunoglobulin or membrane Fc or C3-receptor reactions3,4. Furthermore, migration inhibitory activity has been found in the long term culture supernatants of some established lymph…