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1.

Background

Mitochondrial biogenesis is crucial for myogenic differentiation and regeneration of skeletal muscle tissue and is tightly controlled by the peroxisome proliferator-activated receptor-γ co-activator 1 (PGC-1) signaling network. In the present study, we hypothesized that inactivation of glycogen synthase kinase (GSK)-3β, previously suggested to interfere with PGC-1 in non-muscle cells, potentiates PGC-1 signaling and the development of mitochondrial biogenesis during myogenesis, ultimately resulting in an enhanced myotube oxidative capacity.

Methods

GSK-3β was inactivated genetically or pharmacologically during myogenic differentiation of C2C12 muscle cells. In addition, m. gastrocnemius tissue was collected from wild-type and muscle-specific GSK-3β knock-out (KO) mice at different time-points during the reloading/regeneration phase following a 14-day hind-limb suspension period. Subsequently, expression levels of constituents of the PGC-1 signaling network as well as key parameters of mitochondrial oxidative metabolism were investigated.

Results

In vitro, both knock-down as well as pharmacological inhibition of GSK-3β not only increased expression levels of important constituents of the PGC-1 signaling network, but also potentiated myogenic differentiation-associated increases in mitochondrial respiration, mitochondrial DNA copy number, oxidative phosphorylation (OXPHOS) protein abundance and the activity of key enzymes involved in the Krebs cycle and fatty acid β-oxidation. In addition, GSK-3β KO animals showed augmented reloading-induced increases in skeletal muscle gene expression of constituents of the PGC-1 signaling network as well as sub-units of OXPHOS complexes compared to wild-type animals.

Conclusion

Inactivation of GSK-3β stimulates activation of PGC-1 signaling and mitochondrial biogenesis during myogenic differentiation and reloading of the skeletal musculature.  相似文献   
2.
Several new molecules with different thio-scaffolds were designed, synthesised, and evaluated biologically as inhibitors of Carbonic Anhydrases (CAIs). The structure-activity relationship analysis identified thioether derivatives, here reported, as a potent and selective CAIs against hCA II and hCA IX. High resolution X-ray structure of inhibitor bound hCA II revealed extensive interactions with the hydrophobic pocket of active site and provided molecular insight into the binding properties of these new inhibitors.  相似文献   
3.
4.
污染区域大气环境质量生物监测的数学模式   总被引:2,自引:0,他引:2  
以常规标准取样法、静态挂片吸收取样法分别测定了深圳南山区范围内大气二氧化硫、硫酸盐化速率和氟化物的含量,并同步测定了植物叶片的污染物含量。利用回归方法分析了3种测定结果的相互关系,并以植物叶片污染物含量为基础建立大气环境质量生物监测的数学模型,其中以叶片含硫量评价大气硫酸盐化速率的模型为夏季y=0.781x-0.754,冬季y=1.88x-2.283;以叶片含氟量评价大气氟化物的模型为夏季y=0.363x-7.511,冬季y=0.175x-3.461,这些模型均有很高的可信度(p<0.001)。  相似文献   
5.
To explore new scaffolds for the treat of Alzheimer’s disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (124) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.  相似文献   
6.
Summary The effect of sulfur (S) placement and S rate on the efficiency of urea (U) relative to ammonium sulfate (AS) and ammonium nitrate (AN) for cotton were examined in a pot experiment using sandy clay loam soil (pH 7.9). The results showed that AS and AN application in the absence of S increased the yield than U partly because U-induced damage to plants. The combined application of the N sources with S increased the yields and that, the placement of S in the seed horizon in contact with N was more effective than mixing throughout the soil especially with U. These effects were observed with three cotton cultivars. The addition of S to a maximum of 1.5 g/pot gave further increases in yields or the N content of leaves for U, AS or AN. Using the least squares method, it was found that the presence of S significantly increased the efficiency of U than AS or AN. Incubation of S and the N sources with S in the soil was carried out to understand the growth conditions of cotton fertilized by U in alkalin soil. In the case of U-soil system, the pH increased. NO2−N accumulated and considerable loss of N took place. The pH, NO2−N accumulation and the loss of N decreased with S increments.  相似文献   
7.
1-Naphthalenesulfonate (1-NS) was utilized by axenic cultures of Scenedesmus obliquus and by 5 other green microalgae as the sole source of sulfur. For all algae under study, 2-naphthalenesulfonate was definitely inferior to 1-NS as a source of sulfur. The rate of disapperance of 1-NS from the medium was measured by HPLC and, indirectly, by relating growth to sulfur supply. The physiological availability of 1-NS sulfur for Scenedesmus obliquus amounted to about 14% of sulfate sulfur. 1-Naphthol appeared as the major metabolite of 1-NS. Hence, it was concluded that 1-NS underwent a desulfonation which also took place in the presence of moderate concentrations of sulfate.Abbreviations HPLC high performance liquid chromatography - 1-NS 1-naphthalenesulfonic acid - 2-NS 2-naphthalenesulfonic acid - OD optical density - OD0 optical density at time 0 of the light-and-dark cycle Dedicated to Prof. Dr. W. Habsguth on the occasion of his 75th birthday  相似文献   
8.
H2S, the most recently discovered gasotransmitter, might in fact be the evolutionary matriarch of this family, being both ancient and highly reduced. Disruption of γ-cystathionase in mice leads to cardiovascular dysfunction and marked hypertension, suggesting a key role for this enzyme in H2S production in the vasculature. However, patients with inherited deficiency in γ-cystathionase apparently do not present vascular pathology. A mitochondrial pathway disposes sulfide and couples it to oxidative phosphorylation while also exposing cytochrome c oxidase to this metabolic poison. This report focuses on the biochemistry of H2S biogenesis and clearance, on the molecular mechanisms of its action, and on its varied biological effects.  相似文献   
9.
研究了我国北方地区主要轮作制度下,土壤一植物生态系统中硫的主要输入(归还)与输出(攫取)途径.结果表明,在我国北方普遍推行的小麦-玉米轮作制中,作物收获物从土壤中攫取的硫素总量为每年26.4kg·hm^-2,由根系和植物其它残留物归还给土壤的硫素为每年6.8kg·hm^-2;在小麦.大豆轮作制中。作物收获物从土壤中攫取的硫素总量为每年24.4kg·hm^-2,对土壤的归还量为每年7.2kg·hm^-2;而在玉米-油菜轮作制中,收获物从土壤中攫取的硫量为每年45.4kg·hm^-2,归还给土壤的硫量为每年8.7kg·hm^-2;其它作物如棉花、高粱、花生、水稻种植一季通过收获物从土壤中带走的硫量分别为每年7.9、6.4、6.7和18.9kg·hm^-2。对土壤的归还量分别为每年2.6、1.8、4.3和5.6kg·hm^-2.通过对系统主要输入输出通量的估算,几种主要农田生态系统硫盈亏的状况计算结果说明,供试作物皆存在硫亏缺状况:小麦每年6kg·hm^-2、玉米8.5kg·hm^-2、油菜24kg·hm^-2、水稻7.1kg·hm^-2.  相似文献   
10.
Abstract: Hyperthermophiles are a recently discovered group of microorganisms that grow at and above 90°C. They currently comprise over 20 different genera, and except for two novel bacteria, all are classified as Archaea. The majority of these organisms are obligately anaerobic heterotrophs that reduce elemental sulfur (S°) to H2S. The best studied from a biochemical perspective are the archaeon, Pyrococcus furiosus , and the bacterium, Thermotoga maritima , both of which are saccharolytic. P. furiosus is thought to contain a new type of Entner-Doudoroff pathway for the conversion of carbohydrates ultimately to acetate, H2 and CO2. The pathway is independent of nicotinamide nucleotides and involves novel types of ferredoxin-linked oxidoreductases, one of which has tungsten, a rarely used element, as a prosthetic group. The only site of energy conservation is at the level of acetyl CoA, which in the presence of ADP and phosphate is converted to acetate and ATP in a single step. In contrast, T. maritima utilizes a conventional Embden-Meyerhof pathway for sugar oxidation. P. furiosus also utilizes peptides as a sole carbon and energy source. Amino acid oxidation is thought to involve glutamate dehydrogenase together with at least three types of novel ferredoxin-linked oxidoreductases which catalyze the oxidation of 2-ketoglutarate, aryl pyruvates and formaldehyde. One of these enzymes also utilizes tungsten. In P. furiosus , virtually all of the reductant that is generated during the catabolism of both carbohydrates and peptides is channeled to a cytoplasmic hydrogenase. This enzyme is now termed sulhydrogenase, as it reduces both protons to H2 and S°(or polysulfide) to H2S. S° reduction appears to lead to the conservation of energy in P. furiosus but not in T. maritima , although the mechanism by which this occurs is not known.  相似文献   
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