NAD(P)H Dehydrogenase (Quinone)
HSP90 Heat-Shock Proteins
Metals, Alkaline Earth
Electron Transport Complex II
Chromatography, High Pressure Liquid
Magnetic Resonance Spectroscopy
Indicators and Reagents
Electron Spin Resonance Spectroscopy
p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function. (1/2081)Genetic screens in Drosophila have identified p50(cdc37) to be an essential component of the sevenless receptor/mitogen-activated kinase protein (MAPK) signaling pathway, but neither the function nor the target of p50(cdc37) in this pathway has been defined. In this study, we examined the role of p50(cdc37) and its Hsp90 chaperone partner in Raf/Mek/MAPK signaling biochemically. We found that coexpression of wild-type p50(cdc37) with Raf-1 resulted in robust and dose-dependent activation of Raf-1 in Sf9 cells. In addition, p50(cdc37) greatly potentiated v-Src-mediated Raf-1 activation. Moreover, we found that p50(cdc37) is the primary determinant of Hsp90 recruitment to Raf-1. Overexpression of a p50(cdc37) mutant which is unable to recruit Hsp90 into the Raf-1 complex inhibited Raf-1 and MAPK activation by growth factors. Similarly, pretreatment with geldanamycin (GA), an Hsp90-specific inhibitor, prevented both the association of Raf-1 with the p50(cdc37)-Hsp90 heterodimer and Raf-1 kinase activation by serum. Activation of Raf-1 via baculovirus coexpression with oncogenic Src or Ras in Sf9 cells was also strongly inhibited by dominant negative p50(cdc37) or by GA. Thus, formation of a ternary Raf-1-p50(cdc37)-Hsp90 complex is crucial for Raf-1 activity and MAPK pathway signaling. These results provide the first biochemical evidence for the requirement of the p50(cdc37)-Hsp90 complex in protein kinase regulation and for Raf-1 function in particular. (+info)
Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (2/2081)Activation of the extracellularly regulated kinase (ERK) pathway is part of the early biochemical events that follow lipopolysaccharide (LPS) treatment of macrophages or their infection by virulent and attenuated Salmonella strains. Phagocytosis as well as the secretion of invasion-associated proteins is dispensable for ERK activation by the pathogen. Furthermore, the pathways used by Salmonella and LPS to stimulate ERK are identical, suggesting that kinase activation might be solely mediated by LPS. Both stimuli activate ERK by a mechanism involving herbimycin-dependent tyrosine kinase(s) and phosphatidylinositol 3-kinase. Phospholipase D activation and stimulation of protein kinase C appear to be intermediates in this novel pathway of MEK/ERK activation. (+info)
Involvement of tyrosine phosphorylation in HMG-CoA reductase inhibitor-induced cell death in L6 myoblasts. (3/2081)Our previous studies have shown that the HMG-CoA reductase (HCR) inhibitor (HCRI), simvastatin, causes myopathy in rabbits and kills L6 myoblasts. The present study was designed to elucidate the molecular mechanism of HCRI-induced cell death. We have demonstrated that simvastatin induces the tyrosine phosphorylation of several cellular proteins within 10 min. These phosphorylations were followed by apoptosis, as evidenced by the occurrence of internucleosomal DNA fragmentation and by morphological changes detected with Nomarski optics. Simvastatin-induced cell death was prevented by tyrosine kinase inhibitors. The MTT assay revealed that the addition of mevalonic acid into the culture medium partially inhibited simvastatin-induced cell death. Thus, these results suggested that protein tyrosine phosphorylation might play an important role in the intracellular signal transduction pathway mediating the HCRI-induced death of myoblasts. (+info)
Role of a novel photosystem II-associated carbonic anhydrase in photosynthetic carbon assimilation in Chlamydomonas reinhardtii. (4/2081)Intracellular carbonic anhydrases (CA) in aquatic photosynthetic organisms are involved in the CO2-concentrating mechanism (CCM), which helps to overcome CO2 limitation in the environment. In the green alga Chlamydomonas reinhardtii, this CCM is initiated and maintained by the pH gradient created across the chloroplast thylakoid membranes by photosystem (PS) II-mediated electron transport. We show here that photosynthesis is stimulated by a novel, intracellular alpha-CA bound to the chloroplast thylakoids. It is associated with PSII on the lumenal side of the thylakoid membranes. We demonstrate that PSII in association with this lumenal CA operates to provide an ample flux of CO2 for carboxylation. (+info)
Inactivation of both RNA binding and aconitase activities of iron regulatory protein-1 by quinone-induced oxidative stress. (5/2081)Iron regulatory protein-1 (IRP-1) controls the expression of several mRNAs by binding to iron-responsive elements (IREs) in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. IRE binding activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2. Here, we study the effects of intracellular quinone-induced oxidative stress on IRP-1. Treatment of murine B6 fibroblasts with menadione sodium bisulfite (MSB), a redox cycling drug, causes a modest activation of IRP-1 to bind to IREs within 15-30 min. However, IRE binding drops to basal levels within 60 min. Surprisingly, a remarkable loss of both IRE binding and aconitase activities of IRP-1 follows treatment with MSB for 1-2 h. These effects do not result from alterations in IRP-1 half-life, can be antagonized by the antioxidant N-acetylcysteine, and regulate IRE-containing mRNAs; the capacity of iron-starved MSB-treated cells to increase transferrin receptor mRNA levels is inhibited, and MSB increases the translation of a human growth hormone indicator mRNA bearing an IRE in its 5'-untranslated region. Nonetheless, MSB inhibits ferritin synthesis. Thus, menadione-induced oxidative stress leads to post-translational inactivation of both genetic and enzymatic functions of IRP-1 by a mechanism that lies beyond the "classical" Fe-S cluster switch and exerts multiple effects on cellular iron metabolism. (+info)
Stimulation of ultraviolet-induced apoptosis of human fibroblast UVr-1 cells by tyrosine kinase inhibitors. (6/2081)Damnacanthal is an anthraquinone compound isolated from the root of Morinda citrifolia and was reported to have a potent inhibitory activity towards tyrosine kinases such as Lck, Src, Lyn and EGF receptor. In the present study, we have examined the effects of damnacanthal on ultraviolet ray-induced apoptosis in ultraviolet-resistant human UVr-1 cells. When the cells were treated with damnacanthal prior to ultraviolet irradiation, DNA fragmentation was more pronounced as compared to the case of ultraviolet irradiation alone. The other tyrosine kinase inhibitors, herbimycin A and genistein, also caused similar effects on ultraviolet-induced apoptosis but to a lesser extent. Serine/threonine kinase inhibitors, K252a, staurosporine and GF109203X, rather suppressed the ultraviolet-induced DNA cleavage. Immunoblot analysis showed that pretreatment with damnacanthal followed by ultraviolet irradiation increased the levels of phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases. However, the other tyrosine kinase inhibitors did not increase the phosphorylation of extracellular signal-regulated kinases but stimulated phosphorylation of stress-activated protein kinases. Consequently, the ultraviolet-induced concurrent increase in both phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases after pretreatment with damnacanthal might be characteristically related to the stimulatory effect of damnacanthal on ultraviolet-induced apoptosis. (+info)
Effects of pyrogallol, hydroquinone and duroquinone on responses to nitrergic nerve stimulation and NO in the rat anococcygeus muscle. (7/2081)1. The hypothesis that endogenous superoxide dismutase (SOD) protects the nitrergic transmitter from inactivation by superoxide and that this explains the lack of sensitivity of the transmitter to superoxide generators was tested in the rat isolated anococcygeus muscle. 2. Responses to nitrergic nerve stimulation or to NO were not significantly affected by exogenous SOD or by the Cu/Zn SOD inhibitor diethyldithiocarbamic acid (DETCA). 3. Hydroquinone produced a concentration-dependent reduction of responses to NO with an IC50 of 27 microM, and higher concentrations reduced relaxant responses to nitrergic nerve stimulation with an IC50 of 612 microM. The effects of hydroquinone were only slightly reversed by SOD, so it does not appear to be acting as a superoxide generator. 4. Pyrogallol produced a concentration-dependent reduction in responses to NO with an IC50 value of 39 microM and this effect was reversed by SOD (100-1000 u ml(-1)). Pyrogallol did not affect responses to nitrergic nerve stimulation. Treatment with DETCA did not alter the differentiating action of pyrogallol. 5. Duroquinone produced a concentration-dependent reduction of relaxations to NO with an IC50 value of 240 microM and 100 microM slightly decreased nitrergic relaxations. After treatment with DETCA, duroquinone produced greater reductions of relaxant responses to NO and to nitrergic stimulation, the IC50 values being 8.5 microM for NO and 40 microM for nitrergic nerve stimulation: these reductions were reversed by SOD. 6. The findings do not support the hypothesis that the presence of Cu/Zn SOD explains the greater susceptibility of NO than the nitrergic transmitter to the superoxide generator pyrogallol, but suggest that it may play a role in the effects of duroquinone. (+info)
Tyrosine kinase-dependent modulation by interferon-alpha of the ATP-sensitive K+ current in rabbit ventricular myocytes. (8/2081)We examined the effects of interferon-alpha on the ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells using the patch-clamp technique. IK,ATP was induced by NaCN. Whole-cell experiments indicated that interferon-alpha (5 x 10(2) - 2.4 x 10(4) U/ml) inhibited IK,ATP in a concentration-dependent manner (60.7+/-7.5% with 2.4 x 10(4) U/ml). In cell-attached configuration, interferon-alpha (2.4 x 10(4) U/ml) applied to the external solution also inhibited the activity of the single ATP-sensitive K+ (KATP) channel by 56.0+/-5.8% without affecting the single channel conductance. The inhibitory effect of IK,ATP by interferon-alpha was blocked by genistein and herbimycin A, tyrosine kinase inhibitors, but was not affected by N-(2-metylpiperazyl)-5-isoquinolinesulfoamide (H-7), an inhibitor of protein kinase C and cAMP-dependent protein kinase. These findings suggest that interferon-alpha inhibits the cardiac KATP channel through the activation of tyrosine kinase. The tyrosine kinase-mediated inhibition of IK,ATP by cytokines may aggravate cell damage during myocardial ischemia. (+info)
The Leukemia L5178 cell line has been used in numerous studies to investigate the molecular mechanisms underlying cancer development and progression. For example, researchers have used these cells to study the role of specific genes and proteins in tumorigenesis, as well as the effects of environmental factors such as radiation and chemical carcinogens on cancer development.
In addition to its use in basic research, the Leukemia L5178 cell line has also been used as a model system for testing the efficacy of new anti-cancer drugs. These cells are often implanted into mice and then treated with different drug regimens to assess their ability to inhibit tumor growth and induce apoptosis (programmed cell death).
Overall, the Leukemia L5178 cell line is a valuable tool for cancer researchers, providing a reliable and well-characterized model system for studying various aspects of cancer biology. Its use has contributed significantly to our understanding of the molecular mechanisms underlying cancer development and progression, and has helped to identify potential therapeutic targets for the treatment of this disease.
P-benzoquinone reductase (NADPH)
Reduction of nitro compounds
Potassium hydrogen phthalate
Lee Irvin Smith
p-Benzoquinone dioxime 10502-T
2,5-Dimethyl-1,4-benzoquinone | LGC Standards
Rule VT 01 00: monothio-o-benzoquinone/benzoxathiete
Benzoquinones and Terphenyl Compounds As Phosphodiesterase-4B Inhibitors from a Fungus of the Order Chaetothyriales (MSX 47445)...
Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism - PubMed
TR-179: p-Benzoquinone dioxime (105-11-3) | Chemical Effects in Biological Systems
Oxalic acid-Lifechemical|1,4 Naphthoquinone|Flame retardant DDP|Polyaluminium Chloride|Anthraquinone|benzoquinone
p-Benzoquinone dioxime: Target Organs and Levels of Evidence for TR-179
CDC - Immediately Dangerous to Life or Health Concentrations (IDLH): Quinone - NIOSH Publications and Products
"Biological Activity and Solubility of 5-Methoxy-1,4-Benzoquinone Havin" by Siti Mariyah Ulfa, Fath Dwisari et al.
Millipede toxin: MedlinePlus Medical Encyclopedia
Mitarbeitende - Eawag
NHANES 1999-2000: Cholesterol - LDL & Triglycerides Data Documentation, Codebook, and Frequencies
Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel...
NIOSHTIC-2 Search Results - Full View
UFZ - Publication Index - Helmholtz-Centre for Environmental Research
MedlinePlus - Search Results for: HYDROQUINONE OR OCTINOXATE
Alkaptonuria (Black Urine Disease) Differential Diagnoses
Lecture Video 2 of Principles and Applications of Electron Paramagnetic Resonance Spectroscopy. by Prof Ranjan Das of Other...
Dyes Intermediates - Dyes Intermediate supplier,manufacturer,exporter
Publication Year: 2017 / Subject: chemical structure / Subject term: chemical structure / Text Availability: Citation in PubAg ...
Acetaminophen Toxicity Workup: Approach Considerations, Rumack-Matthew Nomogram, Anion Gap
Pure and Applied Chemistry
- Albumin adducts of benzene oxide (BO-Alb) and 1,4-benzoquinone (1,4-BQ-Alb) were investigated among 134 workers exposed to benzene and 51 unexposed controls in Tianjin, China. (nih.gov)
- Liquid chromatography-mass spectrometry was used to determine the reactivity of the model electrophiles para-benzoquinone, hydroquinone, and 1,4-naphthoquinone with deoxynucleoside (deoxyadenosine (dA), deoxyguanosine (dG), deoxycytidine (dC) and thymidine (dT)) to detect formation of adducts via constant neutral loss scan of deoxyribose (116 Da), and to elucidate adduct structures using high resolution mass spectrometry. (ufz.de)
- Three of the adducts formed by benzoquinone have not been reported before. (ufz.de)
- Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives' allergenicity. (cdc.gov)
- Benzoquinones fused to heterocycles, like most benzoquinones, have the potential for a wide-array of applications but their inherent reactivity can present a synthetic dilemma. (heterocycles.jp)
- Acetaminophen crosses the placenta, and the fetal liver is able to elaborate the hepatotoxic metabolite of APAP, N -acetyl-p-benzoquinone imine (NAPQI), by 14 weeks' gestation. (medscape.com)
- The metal-independent production of hydroxyl radicals (*OH) from H(2)O(2) and tetrachloro-1,4-benzoquinone (TCBQ), a carcinogenic metabolite of the widely used wood-preservative pentachlorophenol, was studied by electron spin resonance methods. (oregonstate.edu)
- Abstract: Coenzyme Q10 (CoQ10) is a small lipophillic molecule composed of a benzoquinone ring and a hydrophobic isoprenoid tail and is present in virtually all cell membranes. (nih.gov)
- Raxone is a synthetic short-chain benzoquinone and an enzyme NAD(P)H: Quinone Oxidoreductase 1 (NQO1) cofactor. (pharmaceutical-technology.com)
- Lown, J. W. Formation of Benzoxathiete under Mild Conditions and Its Valence Tautomerism in Solution to Monothio-o-Benzoquinone: An Experimental and Quantum Chemical Study. (nih.gov)
- Eleven antipyrine/pyridazinone hybrids were synthesized and evaluated for their in vivo analgesic and anti-inflammatory activities by p-benzoquinone-induced writhing test and carrageenan-induced paw edema model, respectively. (tubitak.gov.tr)
- Inhibition of human DNA topoisomerase II by hydroquinone and p-benzoquinone, reactive metabolites of benzene. (nih.gov)
- In vitro treatments with the benzene metabolites hydroquinone, 1,4-benzoquinone, phenol, and catechol resulted in significant increases in micronuclei formation. (nih.gov)
- Phenol, catechol, and 1,4-benzoquinone treatments resulted in moderate (2- to 5-fold) increases in micronuclei, whereas hydroquinone treatments resulted in a larger (11-fold) increase in micronuclei. (nih.gov)
- Significant dose-related increases in kinetochore-positive micronucleated cells were not observed following 1,4-benzoquinone treatment but were observed following treatment with phenol, catechol, and hydroquinone. (nih.gov)
- The higher efficacy of hydroquinone in inducing both total micronuclei and kinetochore-positive micronucleated cells when compared with catechol, phenol, and 1,4-benzoquinone suggests that hydroquinone is a major contributor to the clastogenicity and aneuploidy observed in the lymphocytes of benzene-exposed workers. (nih.gov)
- 2. MSC, a new benzoquinone-containing natural product with antimetastatic effect. (nih.gov)