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Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction. 总被引:11,自引:0,他引:11
Kwon Moo Park Cornelis Kramers Muriel Vayssier-Taussat Ang Chen Joseph V Bonventre 《The Journal of biological chemistry》2002,277(3):2040-2049
Protection against ischemic kidney injury is afforded by 24 h of ureteral obstruction (UO) applied 6 or 8 days prior to the ischemia. Uremia or humoral factors are not responsible for the protection, since unilateral UO confers protection on that kidney but not the contralateral kidney. Prior UO results in reduced postischemic outer medullary congestion and leukocyte infiltration. Prior UO results in reduced postischemic phosphorylation of c-Jun N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6. Very few cells stain positively for proliferating cell nuclear antigen after obstruction, indicating that subsequent protection against ischemia is not related to proliferation with increased numbers of newly formed daughter cells more resistant to injury. UO increases the expression of heat shock protein (HSP)-25 and HSP-72. The increased HSP-25 expression persists for 6 or 8 days, whereas HSP-72 does not. HSP-25 expression is increased in the proximal tubule cells in the outer stripe of the outer medulla postobstruction, prior to, and 24 h after ischemia. In LLC-PK(1) renal epithelial cells, adenovirus-expressed human HSP-27 confers resistance to chemical anoxia and oxidative stress. Increased HSP-27 expression in LLC-PK(1) cells results in reduced H(2)O(2)-induced phosphorylation of JNK1/2 and p38. In conclusion, prior transient UO renders the kidney resistant to ischemia. This resistance to functional consequences of ischemia is associated with reduced postischemic activation of JNK, p38 MAP kinases, and their upstream MAPK kinases. The persistent increase in HSP-25 that occurs as a result of UO may contribute to the reduction in phosphorylation of MAPKs that have been implicated in adhesion molecule up-regulation and cell death. 相似文献
23.
Chemokines were described originally in the context of providing migrational cues for leukocytes. They are now known to have broader activities, including those that favor tumor growth. We addressed whether and which chemokines may be important promoters of the growth of the incurable brain neoplasm, malignant gliomas. Analyses of 16 human glioma lines for the expression of chemokine receptors belonging to the CXCR and CCR series revealed low to negligible levels of all receptors, with the exception of CXCR4 that was expressed by 13 of 16 lines. All six resected human glioma specimens showed similarly high CXCR4 expression. The CXCR4 on glioma lines is a signaling receptor in that its agonist, stromal cell-derived factor-1 (SDF-1; CXCL12), produced rapid phosphorylation of mitogen-activated protein kinases. Furthermore, SDF-1 induced the phosphorylation of Akt (protein kinase B), a kinase associated with survival, and prevented the apoptosis of glioma cells when serum was withdrawn from the culture medium. SDF-1 also mediated glioma chemotaxis, in accordance with this better known role of chemokines. We conclude that glioma cells express a predominant chemokine receptor, CXCR4, and that this functions to regulate survival in part through activating pathways such as Akt. 相似文献
24.
Ben Khalaf N De Muylder G Ratnam J Kean-Hooi Ang K Arkin M McKerrow J Chenik M 《Journal of biomolecular screening》2011,16(5):545-551
The use of a high-throughput technique to perform a pilot screen for Leishmania major protein disulfide isomerase (LmPDI) inhibitors identification is reported. In eukaryotic cells, protein disulfide isomerase (PDI) plays a crucial role in protein folding by catalyzing the rearrangement of disulfide bonds in substrate proteins following their synthesis. LmPDI displays similar domain structure organization and functional properties to other PDI family members and is involved in Leishmania virulence. The authors used a method based on the enzyme-catalyzed reduction of insulin in the presence of dithiothreitol. The screen of a small library of 1920 compounds was performed in a 384-well format and led to the identification of 27 compounds with inhibitory activity against LmPDI. The authors further tested the cytotoxicity of these compounds using Jurkat cells as well as their effect on Leishmania donovani amastigotes using high-content analysis. Results show hexachlorophene and a mixture of theaflavin monogallates inhibit Leishmania multiplication in infected macrophages derived from THP-1 cells, although the inhibitory effect on LmPDI enzymatic activity does not necessarily correlate with the antileishmanial activity. 相似文献
25.
Youyun Liang Tong Si Ee Lui Ang Huimin Zhao 《Applied and environmental microbiology》2014,80(21):6677-6684
Several yeast strains have been engineered to express different cellulases to achieve simultaneous saccharification and fermentation of lignocellulosic materials. However, successes in these endeavors were modest, as demonstrated by the relatively low ethanol titers and the limited ability of the engineered yeast strains to grow using cellulosic materials as the sole carbon source. Recently, substantial enhancements to the breakdown of cellulosic substrates have been observed when lytic polysaccharide monooxygenases (LPMOs) were added to traditional cellulase cocktails. LPMOs are reported to cleave cellulose oxidatively in the presence of enzymatic electron donors such as cellobiose dehydrogenases. In this study, we coexpressed LPMOs and cellobiose dehydrogenases with cellobiohydrolases, endoglucanases, and β-glucosidases in Saccharomyces cerevisiae. These enzymes were secreted and docked onto surface-displayed miniscaffoldins through cohesin-dockerin interaction to generate pentafunctional minicellulosomes. The enzymes on the miniscaffoldins acted synergistically to boost the degradation of phosphoric acid swollen cellulose and increased the ethanol titers from our previously achieved levels of 1.8 to 2.7 g/liter. In addition, the newly developed recombinant yeast strain was also able to grow using phosphoric acid swollen cellulose as the sole carbon source. The results demonstrate the promise of the pentafunctional minicellulosomes for consolidated bioprocessing by yeast. 相似文献
26.
Natalie K.Y. Wee Ivana Vrhovac Madunic Tonci Ivanisevic Benjamin P Sinder Ivo Kalajzic 《Journal of musculoskeletal & neuronal interactions》2020,20(4):579
Objectives:Neuropeptide Y (NPY) is involved in the coordination of bone mass and adiposity. However, multiple NPY sources exist and their individual contribution to the skeleton and adiposity not known. The objectives of our study were to evaluate the effects of peripheral mesenchymal derived NPY to the skeleton and adiposity and to compare them to the global NPYKO model.Methods:To study the role of mesenchymal-derived NPY, we crossed conditional NPY (NPYfl/fl) mice with Prx1cre to generate PrxNPYKO mice. The bone phenotype was assessed using micro-CT. The skeletal phenotype of PrxNPYKO mice was subsequently compared to global NPYKO model. We evaluated body weight, adiposity and functionally assessed the feeding response of NPY neurons to determine whether central NPY signaling was altered by Prx1cre.Results:We identified the increase in cortical parameters in PrxNPYKO mice with no changes to cancellous bone. This was the opposite phenotype to global NPYKO mice generated from the same conditional allele. Male NPYKO mice have increased adiposity, while PrxNPYKO mice showed no difference, demonstrating that local mesenchymal-derived NPY does not influence adiposity.Conclusion:NPY mediates both positive and negative effects on bone mass via separate regulatory pathways. Deletion of mesenchymal-derived NPY had a positive effect on bone mass. 相似文献
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28.
Mingbing Zhou Ang Chen Qianqian Zhou Dingqin Tang Heikki Hänninen 《Tree Genetics & Genomes》2017,13(6):129
Transposable elements (transposons) are fragments of DNA sequences which can move within host genome. Miniature inverted-repeat transposable elements (MITEs) are widespread and high-copy transposable elements in eukaryotic genomes. Tourist-like MITEs are especially abundant in plant kingdom. Earlier genome-wide analysis has shown that MITEs are widely distributed in the moso bamboo genome and preferentially inserted into gene regions. In the present study, in order to examine the potential influence of MITEs on the moso bamboo gene expressions, a highly conserved Tourist-like MITE family, which distributed near genes, was selected as research focus and named PhTst-3 (Phyllostachys edulis Tourist-like element 3). The MITEs’ insertion sites were tested in moso bamboo half-sib seedlings by real-time fluorescence quantitative PCR. Amplification polymorphisms were found in a copy of PhTst-3 (PhTst-3-55) which was located in the intron of PH01002699G0010. This inserted PhTst-3-55 had a significant impact on the gene expression revealed by the real-time fluorescence quantitative PCR. The gene expression levels were four times higher in the absence of PhTst-3-55 than those in the presence of it. This finding suggests that the PhTst-3 located in the intron is involved in the regulation of the gene. In order to examine the impact of PhTst-3-55 on the near genes, the PhTst-3-55 was inserted into a promoter analysis vector, pxk7S2D, between the two promoter sequences. The Agrobacterium-mediated transient expression showed that PhTst-3-55 insertion decreases the expression level of upstream GUS gene and downstream GFP gene. So, PhTst-3-55 can have a silencing role by bidirectionally inhibiting gene expression. 相似文献
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【背景】萘普生是一种被广泛使用的非甾体抗炎药,治疗人类疾病的同时对环境产生一定的消极影响,甚至危害到人类的生存环境。【目的】利用微生物降解萘普生类污染物是一种价格低廉且行之有效的方法。【方法】以萘普生为唯一碳源,培养驯化高效的萘普生降解菌群;利用高通量测序技术解析萘普生降解菌群的微生物群落变化,鉴定萘普生降解菌群种类;通过GC-MS分析萘普生降解菌群的降解途径。【结果】获得了以Rhodanobacter为主的萘普生高效降解菌群,确定了萘普生降解菌群的最佳降解条件为:30°C、pH7.0、摇床转速150r/min、接种量10%,萘普生降解率达60.58%,并预测出萘普生降解菌群的降解途径。【结论】获得了高效的萘普生降解菌群,明晰了降解机理和降解途径,不仅丰富了微生物资源种类,更为微生物的工程应用奠定了理论基础。 相似文献