Disease relevance of Lopac-D-5439

• As conflicting results emerged from several studies showing either decreased or increased ROS production during hypoxia, we used experiments mimicking hypoxic intracellular ROS changes by using the redox cycling agent 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), which generates superoxide inside cells [1].
• To focus upon the action of extracellular GSH in preventing H2O2-mediated toxicity, we used 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), which cannot conjugate with GSH but does continuously generate H2O2 through redox cycling [2].
• Exposure of hepatoma 1c1c7 cells to 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) resulted in a sustained elevation of cytosolic Ca2+, DNA single strand breaks and cell killing [3].

High impact information on Lopac-D-5439

• CD4+ T cells were stimulated with anti-CD3 and anti-CD28 mAb in the presence or absence of oxidative stress as supplied by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), which generates a low level of superoxide anion [4].
• Preactivation of RAW 264.7 cells with a nontoxic dose of the redox cycler 2,3-dimethoxy-1,4-naphthoquinone (5 microM) for 15 h attenuated S-nitrosoglutathione (1 mM)-initiated apoptotic cell death and averted accumulation of the tumor suppressor p53, which is indicative for macrophage apoptosis [5].
• Incubation with 0.5 microM staurosporine or 0.3 mM 2,3-dimethoxy-1,4-naphthoquinone induced the characteristic morphologic and biochemical changes of apoptosis [6].
• Rat lung epithelial L2 cells were challenged with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), generates O2.- and H2O2 continuously through redox cycling [7].
• Treatment of cells under hypoxia with low concentrations of the superoxide generator 2,3-dimethoxy-1,4-naphthoquinone lowered HIF-1alpha protein stabilization [8].

Chemical compound and disease context of Lopac-D-5439

• (2) For the experiments, we have used cultured cerebral endothelial cells exposed to hypoxia/reoxygenation or treated with the redox cycling quinone 2,3-Dimethoxy-1,4-naphthoquinone (DMNQ) in the presence or absence of glucose [9].

Biological context of Lopac-D-5439

• PDGFR phosphorylation was also achieved by the redox cycler 2,3-dimethoxy-1,4-naphthoquinone [10].
• Previous studies have shown that the steady-state mRNA level and gene transcription for the catalytic subunit increased in response to the redox-cycling quinone 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in rat lung epithelial L2 cells (M. M. Shi, et al., 1994, J. Biol. Chem. 269,26512-26517) [11].
• Orthovanadate and 2,3-dimethoxy-1,4-naphthoquinone augment growth factor-induced cell proliferation and c-fos gene expression in 3T3-L1 cells [12].
• Striking similarity was observed between VO and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in PI 3-kinase activation, c-fos proto-oncogene expression, and DNA synthesis, key events associated with cell growth [12].

Anatomical context of Lopac-D-5439

• The rate of NAD+ deletion induced by tert-butyl hydroperoxide (500 microM) and 2,3-dimethoxy-1,4-naphthoquinone (50 microM) was reduced by preincubating the hepatocytes for 1 hr with either 3-aminobenzamide (20 mM), nicotinamide (10 mM) or theophylline (7.5 mM), potent inhibitors of poly(ADP-ribose)polymerase [13].
• Lung epithelial cells produce increased reactive oxygen species (ROS) after hypoxia exposure, and they are more susceptible after hypoxia to injury by agents that generate superoxide [O2-; e.g., 2,3-dimethoxy-1,4-naphthoquinone (DMNQ)] [14].
• We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy-1,4-naphthoquinone, that generates H2O2 in cells [15].

Associations of Lopac-D-5439 with other chemical compounds

• Using 4-hydroxy-2-nonenal (4HNE), 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), and tertiary-butylhydroquinone (tBHQ) as models of oxidative stress which are known to work through different mechanisms, we measured changes in cellular GSH, GCL mRNA, and GCL protein [16].
• In the present studies, incubation with the quinones 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) and menadione (MQ), which generate superoxide and hydrogen peroxide, was used to investigate GSH synthesis in bovine pulmonary artery endothelial cells under oxidative stress [17].

Gene context of Lopac-D-5439

• The reactive oxygen species (ROS) donor 2,3-dimethoxy-1,4-naphthoquinone induced MMP-1 secretion and enhanced ANG-II-stimulated MMP-1 expression [18].

References