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991.
992.
Reactive oxygen species (ROS) play important roles in peroxisome proliferator-activated receptor γ (PPARγ) signaling and cell-cycle regulation. However, the PPARγ redox-signaling pathways in lung alveolar epithelial cells remain unclear. In this study, we investigated the in vivo and in vitro effects of PPARγ activation on the levels of lung ROS production and cell-cycle progression using C57BL/6J wild-type and Nox2 knockout mice (n = 10) after intraperitoneal injection of a selective PPARγ agonist (GW1929, 5 mg/kg body wt, daily) for 14 days. Compared to vehicle-treated mice, GW1929 increased significantly the levels of ROS production in wild-type lungs, and this was accompanied by significant up-regulation of PPARγ, Nox2, PCNA, and cyclin D1 and phosphorylation of ERK1/2 and p38MAPK. These effects were absent in Nox2 knockout mice. In cultured alveolar epithelial cells, GW1929 (5 μM for 24 h) increased ROS production and promoted cell-cycle progression from G0/G1 into S and G2/M phases, and these effects were abolished by (1) adding a PPARγ antagonist (BADGE, 1 μM), (2) knockdown of PPARγ using siRNA, or (3) knockout of Nox2. In conclusion, PPARγ activation through Nox2-derived ROS promotes cell-cycle progression in normal mouse lungs and in cultured normal alveolar epithelial cells. 相似文献
993.
Biological denitrification reaction can be achieved under aerobic environment. Few aerobic denitrifiers using nitrite as sole nitrogen source were identified. Using nitrite as the sole nitrogen source, this work assessed the denitrification activity of yy7, an aerobic heterotrophic denitrifier identified as Pseudomonas sp. (94% similarity) by 16S rRNA sequencing analysis. The logistic equation describes the cell growth curve, yielding a generation time of 2.9h at an initial 18 mg l(-1)NO(-)?-N. Reduction of NO(-)?-N was primarily achieved during its logarithmic growth phase, and was accompanied by an increase in suspension pH and near complete consumption of dissolved oxygen. Three genes relating to nirK, norB, and nosZ were noted to involve in isolate strain. Isolate yy7 can survive and remove up to 40 mg l(-1)NO(-)?-N and, hence, can be applied as an effective aerobic denitrifier during simultaneous nitrification and denitrification via nitrite processes. 相似文献
994.
995.
996.
Wedellová Z Dietrich J Siklová-Vítková M Kološtová K Kováčiková M Dušková M Brož J Vedral T Stich V Polák J 《Physiological research / Academia Scientiarum Bohemoslovaca》2011,60(1):139-148
Adiponectin is an adipokine increasing glucose and fatty acid metabolism and improving insulin sensitivity. The aim of this study was to investigate the role of adiponectin in the regulation of adipocyte lipolysis. Human adipocytes isolated from biopsies obtained during surgical operations from 16 non-obese and 17 obese subjects were incubated with 1) human adiponectin (20 microg/ml) or 2) 0.5 mM AICAR - activator of AMPK (adenosine monophosphate activated protein kinase). Following these incubations, isoprenaline was added (10(-6) M) to investigate the influence of adiponectin and AICAR on catecholamine-induced lipolysis. Glycerol concentration was measured as lipolysis marker. We observed that adiponectin suppressed spontaneous lipolysis by 21 % and isoprenaline-induced lipolysis by 14 % in non-obese subjects. These effects were not detectable in obese individuals, but statistically significant differences in the effect of adiponectin between obese and non-obese were not revealed by two way ANOVA test. The inhibitory effect of AICAR and adiponectin on lipolysis was reversed by Compound C. Our results suggest, that adiponectin in physiological concentrations inhibits spontaneous as well as catecholamine-induced lipolysis. This effect might be lower in obese individuals and this regulation seems to involve AMPK. 相似文献
997.
Cheng Y Zhang Q Meng Q Xia T Huang Z Wang C Liu B Chen S Xiao F Du Y Guo F 《Molecular endocrinology (Baltimore, Md.)》2011,25(9):1624-1635
We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis. 相似文献
998.
Li YB Xie YY Du NN Lu Y Xu HZ Wang B Yu Y Liu YX Song DQ Chen RX 《Bioorganic & medicinal chemistry letters》2011,21(22):6804-6807
Tuberculosis (TB) is a major health problem worldwide. A series of novel sansanmycin derivatives were designed, semi-synthesized and evaluated for their activity against drug-susceptible Mycobacterium tuberculosis strain H(37)Rv with sansanmycin A (SSA) as the lead. Among these analogs tested, compound 1d possessing an isopropyl group at the amino terminal afforded an increased antimycobacterial activity with a MIC value of 8 μg/mL in comparison with SSA. Importantly, it was active for rifampicin- and isoniazid-resistant M. tuberculosis strain isolated from patients in China. These promising results offer an opportunity for further exploration of this novel class of analogs as antitubercular agents. 相似文献
999.
Koltun E Richards S Chan V Nachtigall J Du H Noson K Galan A Aay N Hanel A Harrison A Zhang J Won KA Tam D Qian F Wang T Finn P Ogilvie K Rosen J Mohan R Larson C Lamb P Nuss J Kearney P 《Bioorganic & medicinal chemistry letters》2011,21(22):6773-6777
A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice. Thus 23c could be another useful tool compound for studying the effects of GCS inhibition in vitro and in vivo. 相似文献
1000.
Narayan S Carlson EM Cheng H Condon K Du H Eckley S Hu Y Jiang Y Kumar V Lewis BM Saxton P Schuck E Seletsky BM Tendyke K Zhang H Zheng W Littlefield BA Towle MJ Yu MJ 《Bioorganic & medicinal chemistry letters》2011,21(6):1634-1638
Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable. 相似文献