Disease relevance of Pyrrolidine dithiocarbamic acid

• Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis [1].
• Treatment of BALENLM 17 and A20 B lymphoma cells or normal murine splenic B lymphocytes with either TPCK or PDTC also resulted in apoptosis [2].
• Pretreatment with pertussis toxin or pyrrolidine dithiocarbamate inhibited complement-dependent IL-6 mRNA expression and IL-6 release, suggesting the involvement of Gi-proteins and nuclear factor-kB (NF-kB) [3].
• In contrast, incubation of alveolar macrophages in the presence of LPS plus the antioxidant pyrrolidine dithiocarbamate, the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, or hypoxia, resulted in near complete inhibition of prostaglandin E2 synthesis, PGHS-2 enzyme synthesis, and gene transcription of PGHS-2 mRNA [4].
• In agreement with this, supplementation of the incubation medium with submicromolar concentrations of copper significantly potentiated pyrrolidine dithiocarbamate toxicity [5].

Psychiatry related information on Pyrrolidine dithiocarbamic acid

• Pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear transcription factor kappa-B (NF-kappaB) and an antioxidant, has beneficial effects in animal models of various diseases, including arthritis, brain ischemia, spinal cord injury, Alzheimer's disease, and Duchenne muscular dystrophy [6].
• Effects of pyrrolidine dithiocarbamate on beta-amyloid (25-35)-induced inflammatory responses and memory deficits in the rat [7].

High impact information on Pyrrolidine dithiocarbamic acid

• Herein, we show that the antioxidants pyrrolidinedithiocarbamate and vitamin E induce apoptosis in CRC cells [8].
• The role of activation of Rel-family binding was demonstrated directly upon addition of the antioxidant pyrrolidinedithiocarbamate, which inhibited the anti-sIg-mediated activation of the endogenous c-myc gene [9].
• NF-kappaB activation and IL-8 secretion were attenuated by the NF-kappaB inhibitors pyrrolidine dithiocarbamate and cell-permeable peptide [10].
• Pyrrolidine dithiocarbamate (an antioxidant inhibitor of NF-kappaB) and catalase partially inhibited CPT-induced DNA fragmentation in granulocytic-differentiated PLB-985 cells, but had no effect in X-CGD cells [11].
• PDTC also markedly attenuated TNF alpha induction of VCAM-1-mediated cellular adhesion [12].

Chemical compound and disease context of Pyrrolidine dithiocarbamic acid

• Pretreatment with pyrrolidine dithiocarbamate or sulfasalazine attenuated the iNOS-dependent production of NO in the lung and restored the normal up-regulation of alveolar fluid clearance by catecholamines after prolonged hemorrhagic shock [13].
• All six anti-inflammatory agents suppressed induction of IL-8 mRNA expression in lung cancer cells by >90%, four (pentoxifylline, celecoxib, pyrrolidine dithiocarbamate, and dexamethasone) having a dose-dependent effect [14].
• In a second study, inhibitors of NF-kappaB [N-acetylcysteine (NAC; 150 mg/kg, b.i.d., i.p.), pyrrolidine dithiocarbamate (PDTC, 50 mg/kg, b. i.d., i.p.)] or vehicle were commenced on day 14 after the onset of proteinuria and were continued until day 30 [15].
• The addition of anti-inflammatory agents pyrrolidine dithiocarbamate, pentoxifylline, aspirin, and dexamethasone could completely suppress the expression of IL-8 mRNA in fresh/sensitized lung cancer cell cocultures [16].
• In addition, the stimulation by NIC of IL-1-induced nitrite production in pyrrolidine dithiocarbamate-treated cells is a novel action that should be considered when the drug is proposed as potential agent for the prevention of insulin-dependent diabetes mellitus [17].

Biological context of Pyrrolidine dithiocarbamic acid

• In cultured human umbilical vein endothelial (HUVE) cells, the cytokine interleukin 1 beta (IL-1 beta) activated VCAM-1 gene expression through a mechanism that was repressed approximately 90% by the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC) [12].
• The presence of z-VAD-fmk and pyrrolidine dithiocarbamate together blocked cell death, suggesting that both apoptotic and necrotic pathways can be activated through the Fas death receptor [18].
• While an inhibitor of protein kinase C could not block gene induction by MHBst, the antioxidants N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) could potently suppress transactivation at mM and microM concentrations, respectively [19].
• The effects were selective because PDTC did not interfere with MHBst and HBx-induced activation of the c-fos promoter/enhancer, nor with the basal activity of several other reporter genes lacking functional NF-kappa B binding motifs [19].
• Activation of AP-1 by PDTC was dependent on protein synthesis and involved transcriptional induction of c-jun and c-fos genes [20].

Anatomical context of Pyrrolidine dithiocarbamic acid

• DNA binding and transactivation by AP-1 were induced in HeLa cells upon treatment with the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC), and upon transient expression of the antioxidative enzyme thioredoxin [20].
• In vivo, rabbits pretreated with PDTC before LPS infusion showed significantly less neutrophil infiltration in the lungs, liver, and heart compared with animals infused with LPS alone [21].
• In human monocytes, the antioxidant pyrrolidine dithiocarbamate (PDTC) rapidly inhibited CCR2 (95-100% of inhibition) and CCR5 (77-100% of inhibition) mRNA expression by strongly decreasing transcript stability [22].
• Pyrrolidine dithiocarbamate abrogates tissue factor (TF) expression by endothelial cells: evidence implicating nuclear factor-kappa B in TF induction by diverse agonists [23].
• To address this question, we have analyzed the effect of pyrrolidine dithiocarbamate (PDTC) on p53 DNA-binding activity in cell lines expressing wild-type p53 [24].

Associations of Pyrrolidine dithiocarbamic acid with other chemical compounds

• Furthermore, PDTC selectively inhibited the induction of VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), mRNA and protein accumulation by the cytokine tumor necrosis factor-alpha (TNF alpha) as well as the noncytokines bacterial endotoxin lipopolysaccharide (LPS) and double-stranded RNA, poly(I:C) (PIC) [12].
• Treatment of WEH1 231 cells with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a protease inhibitor which prevents degradation of the inhibitor of NF-kappaB (IkappaB)-alpha, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF-kappaB/Rel factor binding and induced apoptosis [2].
• In contrast, the ROI-generating system xanthine/xanthine oxidase increased CCR5 and CXCR4 mRNA expression and counteracted the inhibitory effect of PDTC [22].
• Inhibition of ROS in leukemia cells by the antioxidants pyrrolidine dithiocarbamate (PDTC), N-acetylcysteine (NAC), and vitamin E (VE) decreased the mutagenesis rate and frequency of IM resistance [25].
• H-89, dexamethasone, herbimycin, genistein, staurosporine, or pyrrolidine dithiocarbamate (PDTC) attenuated the iNOS induction by LPS [26].

Gene context of Pyrrolidine dithiocarbamic acid

• Pyrrolidine dithiocarbamate, a metal chelator and antioxidant, efficiently inhibited the FADD-induced reduction of DeltaPsim and necrotic cell death [18].
• The PDTC-mediated inhibition of CCR5 and CXCR4 mRNA expression was associated with decreased chemotactic responsiveness (>90% inhibition) and with a marked inhibition of surface-receptor expression [22].
• Pyrrolidine dithiocarbamate inhibits the production of interleukin-6, interleukin-8, and granulocyte-macrophage colony-stimulating factor by human endothelial cells in response to inflammatory mediators: modulation of NF-kappa B and AP-1 transcription factors activity [27].
• Whereas SB203580 inhibited endotoxin-induced NF-kappaB activation, pyrrolidine dithiocarbamate did not affect p38 phosphorylation in endotoxin-stimulated cells [28].
• The action of the antioxidant inhibitor of NF-kappa B activation, pyrrolidine dithiocarbamate, in wild-type and NF-kappa B mutant cells was examined [29].

Analytical, diagnostic and therapeutic context of Pyrrolidine dithiocarbamic acid

• This potentiating effect was mediated by reactive oxygen species (ROS) released by PMN during the coculture; it did not require direct cell contact between PMN and PBMC, it was enhanced when PMN were stimulated by fMLP (a chemotactic peptide), and it was inhibited by two antioxidants, N-acetyl cysteine and pyrrolidine dithiocarbamate [30].
• Electrophoretic mobility shift assay of nuclear extracts from PAEC exposed to human serum revealed an intense NF-kappaB activation that was inhibited by the NF-kappaB inhibitor pyrrolidinedithiocarbamate [31].
• The cAMP analogues potentiated iNOS at the transcriptional level as shown by effects of actinomycin D (5 microgram/ml) and northern blot analyses; the nuclear factor (NF) kappaB inhibitor, pyrrolidine dithiocarbamate (10-200 microM), significantly reduced this potentiation [32].
• In the course of these studies it was discovered that pyrrolidine dithiocarbamate (PDTC) is an extremely potent compound against HRV and poliovirus infection in cell culture [33].
• In the present study using electron spin resonance (ESR) spectroscopy, we evaluated whether pyrrolidine dithiocarbamate (PDTC), a metal chelator and antioxidant, might limit .NO production during the development of rejection in cardiac allografts [34].

References