Showing papers in "Biochemical Pharmacology in 2002"

TL;DR: In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.

TL;DR: It is the aim that this commentary will lead the reader to appreciate that studies investigating the signaling for and regulation of thiol metabolism must never be generalized, and that perturbations in any of step ofThioredoxin and glutathione metabolism may have etiological roles in genetically, virally, and environmentally borne pathologies.

TL;DR: A generic model for the prediction of drug association constants to HSA is reported, which uses a pharmacophoric similarity concept and partial least square analysis (PLS) to construct a quantitative structure-activity relationship.

TL;DR: Observations suggest that NF-kappaB is an ideal target for chemoprevention and chemosensitization and evidence supporting this hypothesis is reviewed.

TL;DR: A model is proposed, that at low concentrations, these compounds activate MAPK pathway leading to activation of Nrf2 and ARE with subsequent induction of phase II and other defensive genes which protect cells against toxic insults thereby enhancing cell survival, a beneficial homeostatic response.

TL;DR: It is proposed that the nucleus represents a site for ERK action, sequestration and signal termination in the MAPK cascade, and it is illustrated that besides controlling cell proliferation the ERK cascade also controls cell differentiation and cell behaviour.

TL;DR: There is a drastic depletion in cytoplasmic levels of the thiol tripeptide glutathione within the SN of PD patients, which might contribute to oxidative stress during PD.

TL;DR: Recent knowledge on the role played by several redox modulators in inducing signalling events that finally regulate cell cycle progression is summarised.

TL;DR: How other posttranslational modifications, such as acetylation and methylation of transcription factors or of the chromatin environment, may also affect NF-κB transcriptional activity is described.

TL;DR: Investigation of potential neuroprotective effects of tea extracts and possible signal pathway involved in a neuronal cell model of Parkinson's disease found brain penetrating property of polyphenols may make such compounds an important class of drugs for treatment of neurodegenerative diseases.

TL;DR: The duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin is described, which may be an attractive new agent for the chemosensitization of cancer cells.

TL;DR: A novel application for resveratrol, a molecule of plant defense, to combat human fungal pathogens is indicated and may have wide application to skin conditions that afflict a significant portion of the authors' population, and may also have promising clinical potentials in diabetic wounds.

TL;DR: The different mechanisms that account for the opposite effects of HIF-1α, as an active transcription factor, can protect cells from apoptosis induced by several conditions are described.

TL;DR: It is confirmed the existence of two of the previously detected polymorphisms which give rise to the amino acid substitutions I264M and K399R, respectively, but failed to detect three others in the authors' population.

TL;DR: It is demonstrated that DIM can induce apoptosis in breast cancer cells independent of estrogen receptor status by a process that is mediated by the modulated expression of the Bax/Bcl-2 family of apoptotic regulatory factors.

TL;DR: The results show that although resveratrol inhibited cell proliferation and viability in both cell lines, apoptosis was induced in a concentration- and cell-specific manner and could take place through the differential regulation of the cell cycle leading to apoptosis or necrosis.

TL;DR: The pharmacological properties of a naturally occurring monoflavonoid, 5,7-dihydroxy-8-methoxyflavone or wogonin, and electrophysiological techniques suggest that wog onin exerts its anxiolytic effect through positive allosteric modulation of the GABA(A) receptor complex via interaction at the BZD-S.

TL;DR: Experiments indicate that a decrease in intracellular peroxide level was involved in wogonin- and fisetin-induced apoptosis; activation of caspase 3 and endonuclease, induction of bax protein and suppression of Mcl-1 protein were detected in the process.

TL;DR: Evidence is provided that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.

TL;DR: It is concluded that hyperforin acts as a dual inhibitor of 5-LO and COX-1 in intact cells as well as on the catalytic activity of the crude enzymes, suggesting therapeutic potential in inflammatory and allergic diseases connected to eicosanoids.

TL;DR: Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5α-reductase inhibitors that were active in both cell-free and whole-cell assay systems, and the presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 α- reductase.

TL;DR: The development of lobeline and lobeline analogs with targeted selectivity at VMAT2 represents a novel class of therapeutic agents having good potential as efficacious treatments for methamphetamine abuse.

TL;DR: The remodelling of chromatin by histone acetylation plays a role in the oxidant-mediated pro-inflammatory responses in the lungs.

TL;DR: Inhibitor structure-activity relationships were investigated to better define the structural requirements for inhibition and to identify points in the molecular topography that could accept polar groups without diminishing inhibition potency, indicating that lipophilicity is an important factor controlling inhibitor potency.

TL;DR: Feeding a high carbohydrate diet induces transcription of more than 15 genes involved in the metabolic conversion of glucose to fat, and a new transcription factor binding to a glucose response element of the pyruvate kinase and lipogenesis enzyme genes was discovered recently.

TL;DR: The prooxidant reactions induced by GSH catabolism appear to represent a novel, as yet unrecognized mechanism for modulation of cellular signal transduction.

TL;DR: A screening of the specificities of rat cytochrome P450 (CYP) isoforms for metabolic reactions known as the specific probes of human CYP isoforms suggests that diclofenac 4-Hydroxylation, dextromethorphan O-demethylation and midazolam 4-hydroxylations are useful as catalytic markers of CYP2C6, CYP3A1/3A2, respectively.

TL;DR: The accumulated information points toward an earlier involvement than previously thought of oxidative stress in the pathogenesis of the disease, making this a potential target for therapeutic intervention, especially in subjects at high risk for developing AD.

TL;DR: Results obtained here support the notion that the mechanisms by which PPARgamma activators and FAs induce transcription of the PEPCK gene are distinct, and argue that several FA effects are PPAR-independent.

TL;DR: It is shown that TCDD and other AHR ligands induced the immediate activation of the extracellular signal-regulated kinases and the Jun N-terminal kinases, but not the p38 MAPKs.