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Over-activation of microglia cells in the brain contributes to neurodegenerative processes promoted by the production of various neurotoxic factors including pro-inflammatory cytokines and nitric oxide. Recently, accumulating evidence has suggested that mitochondrial dynamics are an important constituent of cellular quality control and function. However, the role of mitochondrial dynamics in microglial activation is still largely unknown. In this study, we determined whether mitochondrial dynamics are associated with the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated immortalization of murine microglial cells (BV-2) by a v-raf/v-myc carrying retrovirus (J2). Excessive mitochondrial fission was observed in lentivirus-transfected BV-2 cells stably expressing DsRed2-mito following LPS stimulation. Furthermore, mitochondrial localization of dynamin-related protein 1 (Drp1) (a key regulator of mitochondrial fission) was increased and accompanied by de-phosphorylation of Ser637 in Drp1.Interestingly, inhibition of LPS-induced mitochondrial fission and reactive oxygen species (ROS) generation by Mdivi-1 and Drp1 knock-down attenuated the production of pro-inflammatory mediators via reduced nuclear factor kappa-light-chainenhancer of activated B cells (NF-jB) and mitogen-activated protein kinase (MAPK) signaling. Our results demonstrated for the first time that mitochondrial fission regulates mitochondrial ROS production in activated microglial cells and influences the expression of pro-inflammatory mediators through the activation of NF-jB and MAPK. We therefore suggest that mitochondrial dynamics may be essential for understanding pro-inflammatory mediator expression in activated microglial cells. This could represent a new therapeutic approach for preventing neurodegenerative diseases. Keywords: Drp1, lipopolysaccharide, Mdivi-1, microglia, mitochondrial dynamics, neuroinflammation. Address correspondence and reprint requests to Dong-Seok Lee, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea. E-mail: lee1@knu.ac.kr 1 These authors contributed equally to this work. Abbreviations used: CMVie, cytomegalovirus immediate early; Cox-2, cyclooxygenase-2; COXIV, cytochrome c oxidase; cPPT, central polypurine tract; DMEM, Dulbecco's modified Eagle's medium; Drp1, dynamin-related protein 1; DsRed2, discosoma sp. red fluorescent; ERK, extracellular signal-regulated kinase; FBS, fetal bovine serum; Fis1, mitochondrial fission 1; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; iNOS, inducible nitric oxide synthase; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharide; LTR, long terminal repeat; MAPK, mitogen-activated protein kinase; Mdivi-1, 3-(2,4-dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; Mfn1, mitofusin 1; Mfn2, mitofusin 2; MOI, multiplicity of infection; MTS, mitochondrial targeting sequence; NF-jB, nuclear factor kappa-light-chainenhancer of activated B cells...

This study suggests that ESD might be a feasible treatment technique for small rectal carcinoid tumors. It showed superior efficacy and comparable safety to EMR.

The chromate reductase purified from Pseudomonas ambigua was found to be homologous with several nitroreductases. Escherichia coli DH5␣ and Vibrio harveyi KCTC 2720 nitroreductases were chosen for the present study, and their chromate-reducing activities were determined. A fusion between glutathione Stransferase (GST) and E. coli DH5␣ NfsA (GST-EcNfsA), a fusion between GST and E. coli DH5␣ NfsB (GST-EcNfsB), and a fusion between GST and V. harveyi KCTC 2720 NfsA (GST-VhNfsA) were prepared for their overproduction and easy purification. GST-EcNfsA, GST-EcNFsB, and GST-VhNFsA efficiently reduced nitrofurazone and 2,4,6-trinitrotoluene (TNT) as their nitro substrates. The K m values for GST-EcNfsA, GST-EcNfsB, and GST-VhNfsA for chromate reduction were 11.8, 23.5, and 5.4 M, respectively. The V max values for GST-EcNfsA, GST-EcNfsB, and GST-VhNfsA were 3.8, 3.9, and 10.7 nmol/min/mg of protein, respectively. GST-VhNfsA was the most effective of the three chromate reductases, as determined by each V max /K m value. The optimal temperatures of GST-EcNfsA, GST-EcNfsB, and GST-VhNfsA for chromate reduction were 55, 30, and 30°C, respectively. Thus, it is confirmed that nitroreductase can also act as a chromate reductase. Nitroreductases may be used in chromate remediation. GST-EcNfsA, GST-EcNfsB, and GST-VhNfsA have a molecular mass of 50 kDa and exist as a monomer in solution. Thin-layer chromatography showed that GST-EcNfsA, GST-EcNfsB, and GST-VhNfsA contain FMN as a cofactor. GST-VhNfsA reduced Cr(VI) to Cr(III). Cr(III) was much less toxic to E. coli than Cr(VI).Environmental pollution by chromium may be severe. Chromium contamination is known to be prevalent at U.S. Department of Energy sites (29). The electroplating and leather-tanning industries also contribute to environmental contamination with Cr(VI) (23). Chromate compounds containing Cr(VI) are used widely in the cooling towers of heavy industry and atomic power plants, since Cr(VI) prevents corrosion and the growth of organisms (2). Cr(VI) is soluble, toxic, and carcinogenic, whereas Cr(III) is less soluble and less toxic (12). Thus, it is desirable to change Cr(VI) into Cr(III). This approach is taken in the bioremediation of Cr(VI) pollution. It shows promise for solving pollution problems and has advantages over various other physical and chemical methods.Chromate-reducing activities can be found in the cell extracts of many bacteria (4,5,8,10,13,18,25,30,(33)(34)(35). Chromate reductase can reduce the toxicity of Cr(VI) by reducing it to Cr(III) and lowering its solubility (5, 9). The chromate reductase from Pseudomonas ambigua has been purified and characterized (33). Chromate-reducing activities have been associated with DT-diaphorase (7) and aldehyde oxidase (1) in the cell cytoplasm. Cytochrome P450 located in the cell membrane is also known to have chromate-reducing activity (21). It seems that various reductases in the cell can function in chromate reduction. P. ambigua chromate reductase (33) has high homology with Escherichia coli NfsA (59%) ...

HD (Huntington's disease) is a devastating neurodegenerative genetic disorder caused by abnormal expansion of CAG repeats in the HTT (huntingtin) gene. We have recently established two iPSC (induced pluripotent stem cell) lines derived from a HD patient carrying 72 CAG repeats (HD-iPSC). In order to understand the proteomic profiles of HD-iPSCs, we have performed comparative proteomic analysis among normal hESCs (human embryonic stem cells; H9), iPSCs (551-8) and HD-iPSCs at undifferentiated stages, and identified 26 up- and down-regulated proteins. Interestingly, these differentially expressed proteins are known to be involved in different biological processes, such as oxidative stress, programmed cell death and cellular oxygen-associated proteins. Among them, we found that oxidative stress-related proteins, such as SOD1 (superoxide dismutase 1) and Prx (peroxiredoxin) families are particularly affected in HD-iPSCs, implying that HD-iPSCs are highly susceptible to oxidative stress. We also found that BTF3 (basic transcription factor 3) is up-regulated in HD-iPSCs, which leads to the induction of ATM (ataxia telangiectasia mutated), followed by activation of the p53-mediated apoptotic pathway. In addition, we observed that the expression of cytoskeleton-associated proteins was significantly reduced in HD-iPSCs, implying that neuronal differentiation was also affected. Taken together, these results demonstrate that HD-iPSCs can provide a unique cellular disease model system to understand the pathogenesis and neurodegeneration mechanisms in HD, and the identified proteins from the present study may serve as potential targets for developing future HD therapeutics.

The C-H imidation of arenes and heteroarenes has been achieved via visible light induced photocatalysis. In the presence of an iridium(III) photoredox catalyst, the reaction of aromatic substrates with N-chlorophthalimide furnishes the N-aryl products at room temperature through a nitrogen-centered radical mediated aromatic substitution.

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