Search results for "Ribonucleotides"
showing 10 items of 77 documents
Suppression of the JNK Pathway by Induction of a Metabolic Stress Response Prevents Vascular Injury and Dysfunction
2008
Background— Oxidative injury and dysfunction of the vascular endothelium are early and causal features of many vascular diseases. Single antioxidant strategies to prevent vascular injury have met with mixed results. Methods and Results— Here, we report that induction of a metabolic stress response with adenosine monophosphate kinase (AMPK) prevents oxidative endothelial cell injury. This response is characterized by stabilization of the mitochondrion and increased mitochondrial biogenesis, resulting in attenuation of oxidative c-Jun N-terminal kinase (JNK) activation. We report that peroxisome proliferator coactivator 1α is a key downstream target of AMPK that is both necessary and suffici…
EFFECTS OF DEFIBROTIDE IN PATIENTS WITH CHRONIC DEEP INSUFFICIENCY. THE PROVEDIS STUDY
2004
Aim. In the present study the effect of defibrotide, an antithrombotic and profibrinolytic agent, was investigated in patients with chronic venous insufficiency (CVI) due to deep vein obstruction and/or reflux (chronic deep vein insufficiency, CDVI). Methods. The study was a multicenter, randomized, double blind placebo controlled trial in which only patients with CDVI confirmed by ultrasound were enrolled. All patients were treated with adequate elastic compression and randomized to receive either oral defibrotide (800 mg/die) or matching placebo for 1 year. Patients with active or previous leg ulcer were excluded. Results. A to…
Influence of therapeutic and toxic doses of neuroleptics and antidepressants on energy metabolism of the isolated perfused rat brain.
1973
The isolated perfused rat brain was used for a comparative study of the effects of promazine, imipramine, monodesmethyl promazine and desipramine on cerebral energy metabolism. After perfusion for 30 min or 1 h the brain levels of the following substrates and metabolites were estimated: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, pyruvate, lactate, α-ketoglutarate, and ammonia. Drug concentrations of 5·10−6 M and 10−5 M in the perfusion medium caused a significant decrease of glucose-6-P alone. When the drug concentration was raised to a toxic range (10−4 M), reflected in the EEG by the pattern of secondary discharges, an ac…
Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism
1972
The concentrations of P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, α-glycero-P, lactate and pyruvate were measured in the isolated perfused rat brain as well as in rat brain in vivo. Similar levels were observed in the isolated brain and in intact animals, and the values measured were in good accordance with those described in the literature. Only the pyruvate and lactate content were significantly higher in the isolated brain but the lactate/pyruvate ratio remained unchanged. An anesthetic or ischemia caused just the same effects on energy metabolism of the isolated rat brain as described for intact animals. Thus, 1.5 mM phe…
Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice
2011
Polymorphisms in the transcription factor Stat4 gene have been implicated as risk factors for systemic lupus erythematosus. Although some polymorphisms have a strong association with autoantibodies and nephritis, their impact on pathophysiology is still unknown. To explore this further we used signal transducers and activators of transcription 4 (Stat4) knockout MRL/MpJ-Fas(lpr)/Fas(lpr) (MRL-Fas(lpr)) mice and found that they did not differ in survival or renal function from Stat4-intact MRL-Fas(lpr) mice. Circulating interleukin (IL)-18 levels, however, were elevated in Stat4-deficient compared to Stat4-intact mice, suggesting that this interleukin might contribute to the progression of l…
The membrane distal half of gp130 is responsible for the formation of a ternary complex with IL-6 and the IL-6 receptor
1995
AbstractGp130 is the signal transducing subunit of the interleukin-6 receptor. Signaling is initiated by the complex formation of gp130 with IL-6 bound to the IL-6 receptor (IL-6R). We have subdivided the extracellular domain of gp130 in two parts and expressed the mutant proteins as soluble IgG fusion proteins in COS-7 cells. By studying the formation of the ternary complex we show that the membrane distal half of gp130 which contains a cytokine receptor domain is responsible for the interaction with the IL-6/IL-6R complex. Interestingly this is the same region which is believed to be involved in specific recognition of the related cytokines LIF, OM, and probably also of CNTF and IL-11.
Excessive CpG 1668 stimulation triggers IL-10 production by cDC that inhibits IFN-alpha responses by pDC.
2008
Upon stimulation with a wide range of concentrations of CpG oligodeoxynucleotide 2216 (CpG 2216), plasmacytoid DC are induced to produce type I IFN (IFN-alpha/beta). In contrast, CpG 1668 shows a bell-shaped dose-response correlation, i.e. only intermediate but not high doses of CpG 1668 induce IFN-alpha/beta. Interestingly, high-dose CpG 1668 completely inhibited IFN-alpha responses induced by CpG 2216. Experiments using supernatant of high-dose CpG-1668-treated cells indicated that secreted inhibitor(s) mediated the IFN-alpha shut-off. Among modulating cytokines, IL-10 turned out to be one important negative regulator. In line with this, supernatants of IL-10-deficient DC cultures stimula…
(2'-5')Oligoadenylate and intracellular immunity against retrovirus infection.
1992
1. 1. The double-stranded RNA-dependent 2′,5′-oligoadenylate (2–5A) synthetase/ribonuclease L (RNase L) system plays an essential role in the establishment of the antiviral state of a cell exposed to virus infection. 2. 2. Until recently, the application of 2–5A derivatives to reinforce this system seemed to be limited mainly due to the low specificity of RNase L for viral RNA. 3. 3. Two new strategies have been developed which yield a selective antiviral effect of 2–5As at least against human immunodeficiency virus-1 (HIV-1) infection: (i) an “intracellular immunization” appproach using 2-5A synthetase cDNA linked to HIV trans -acting response element (TAR) and (ii) inhibition of retrovira…
The analysis of modified peroxisome proliferator responsive elements of the peroxisomal bifunctional enzyme in transfected HepG2 cells reveals two re…
1995
AbstractPeroxisome proliferators (PPs) are non-genotoxic carcinogens in rodents. They can induce the expression of numerous genes via the heterodimerization of two members of the steroid hormone receptor superfamily, called the peroxisome proliferator-activated receptor (PPAR) and the 9-cis retinoic acid receptor (RXR). Many of the PP responsive genes possess a peroxisome proliferator response element (PPRE) formed by two TGACCT-related motifs. The bifunctional enzyme (HD) PPRE contains 3 such motifs, creating DR1 and DR2 sequences. PPAR and RXR regulate transcription via the DR1 element while DR2 modulates the expression of the gene via auxiliary factors in HepG2 cells.
Photochemically induced cross-links between DNA and alcohol dehydrogenase or salmine, respectively
1976
Model experiments with two structurally different proteins (alcohol dehydrogenase and salmine) show that glycine, alanine, and tyrosine are by far more frequently involved in photochemically induced cross-link formations with DNA than is cysteine. The yields for cross-link formation of thymidine with salmine (cysteine-free) are about as high as those with alcohol dehydrogenase (a thiol protein).