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191.
Xiuli Zhang Dan Liang Baolei Guo Lixia Sun Zhi-Hong Chi Yuan Cai Lining Wang Jianfei Ma 《Biological trace element research》2013,151(1):138-147
Zinc (Zn) is an essential micronutrient and cytoprotectant involved in preventing many types of epithelial-to-mesenchymal transition (EMT)-driven fibrosis in vivo. The zinc-transporter family SLC30A (ZnT) is a pivotal factor in the regulation of Zn homeostasis. However, its function in EMT in peritoneal mesothelial cells (PMCs) remains unknown. This study explored the regulation of zinc transporters and the role they play in cell EMT, particularly in rat peritoneal mesothelial cells (RPMCs), surrounding glucose concentrations and the molecular mechanism involved. The effects of high glucose (HG) on zinc transporter gene expression were measured in RPMCs by real-time PCR. We explored ZnT7 (Slc30A7): the effect of ZnT7 over-expression and siRNA-mediated knock-down on HG-induced EMT was investigated as well as the underlying molecular mechanisms. Over-expression of ZnT7 resulted in significantly inhibited HG-induced EMT in RPMCs, while inhibition of ZnT7 expression using a considerable siRNA-mediated knock-down of RPMCs increased the levels of EMT. Furthermore, over-expression of ZnT7 is accompanied by down-regulation of TGF-β/Smad pathway, phospho-Smad3,4 expression levels. The finding suggests that the zinc-transporting system in RPMCs is influenced by the exposure to HG. The ZnT7 may account for the inhibition of HG-induced EMT in RPMCs, likely through targeting TGF-β/Smad signaling. 相似文献
192.
The human AAA ATPase p97 is a molecular chaperone essential in cellular proteostasis. Single amino acid substitutions in p97 have been linked to a clinical multiple-disorder condition known as inclusion body myopathy associated with Paget''s disease of the bone and frontotemporal dementia. How the mutations affect the molecular mechanism that governs the function of p97 remains unclear. Here, we show that within the hexameric ring of a mutant p97, D1 domains fail to regulate their respective nucleotide-binding states, as evidenced by the lower amount of prebound ADP, weaker ADP binding affinity, full occupancy of adenosine-5′-O-(3-thiotriphosphate) binding, and elevated overall ATPase activity, indicating a loss of communication among subunits. Defective communication between subunits is further illustrated by altered conformation in the side chain of residue Phe-360 that probes into the nucleotide-binding pocket from a neighboring subunit. Consequently, conformations of N domains in a hexameric ring of a mutant p97 become uncoordinated, thus impacting its ability to process substrate. 相似文献
193.
Je Yeong Ko Kyung Hyun Yoo Seon Ah Song Do Yeon Kim Hyun Kyung Kong Curie Ahn Han Woong Lee Duk-Hee Kang Goo Taeg Oh Jong Hoon Park 《The Journal of biological chemistry》2013,288(9):6488-6497
Cilia in ciliated cells consist of protruding structures that sense mechanical and chemical signals from the extracellular environment. Cilia are assembled with variety molecules via a process known as intraflagellar transport (IFT). What controls the length of cilia in ciliated cells is critical to understand ciliary disease such as autosomal dominant polycystic kidney disease, which involves abnormally short cilia. But this control mechanism is not well understood. Previously, multiple tubular cysts have been observed in the kidneys of max-interacting protein 1 (Mxi1)-deficient mice aged 6 months or more. Here, we clarified the relationship between Mxi1 inactivation and cilia disassembly. Cilia phenotypes were observed in kidneys of Mxi1-deficient mice using scanning electron microscopy to elucidate the effect of Mxi1 on renal cilia phenotype, and cilia disassembly was observed in Mxi1-deficient kidney. In addition, genes related to cilia were validated in vitro and in vivo using quantitative PCR, and Ift20 was selected as a candidate gene in this study. The length of cilium decreased, and p-ERK level induced by a cilia defect increased in kidneys of Mxi1-deficient mice. Ciliogenesis of Mxi1-deficient mouse embryonic fibroblasts (MEFs) decreased, and this abnormality was restored by Mxi1 transfection in Mxi1-deficient MEFs. We confirmed that ciliogenesis and Ift20 expression were regulated by Mxi1 in vitro. We also determined that Mxi1 regulates Ift20 promoter activity via Ets-1 binding to the Ift20 promoter. These results indicate that inactivating Mxi1 induces ciliary defects in polycystic kidney. 相似文献
194.
Ernest Chi Fru Michael Chen Gillian Walshe Tara Penner Christopher Weisener 《Applied microbiology and biotechnology》2013,97(7):3215-3224
Microorganisms in oil sands fluid fine tailings (FFT) are critical to biogeochemical elemental cycling as well as to the degradation of residual hydrocarbon constituents and subsequent methane and CO2 production. Microbial activity enhances particulate matter sedimentation rates and the dewatering of FFT materials, allowing water to be recycled back into bitumen extraction. A bulk of this evidence comes from bioreactor studies and has implications for engineering and environmental management of the FFT ponds. Yet, it is largely uncertain whether such laboratory populations are representative of whole field scale microbial communities. By using population ecology tools, we compared whole microbial communities present in FFT bioreactors to reference populations existing in Syncrude's West In Pit (WIP) tailings pond. Bacteria were found to be persistent in a sulfidic zone in both the oxic and anoxic bioreactors at all occasions tested. In contrast to the WIP, archaea only became predominant in bioreactors after 300 days, at which point analysis of similarity (global R statistic p?<?0.5) revealed no significant dissimilarities between the populations present in either system. A whole community succession pattern from bacterial dominated prevalence to a new assemblage predominated by archaea was suggested. These results have implications for the stepwise development of microbial model systems for predictive management of field scale FFT basins. 相似文献
195.
Sjannie Lefevre Tobias Wang Do Thi Thanh Huong Nguyen Thanh Phuong Mark Bayley 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2013,183(2):215-221
Though air-breathing has probably evolved mainly as a response to hypoxia, it may provide an important oxygen supplement when metabolism is elevated, as for example during swimming. Due to the increased travelling distance involved when an air-breathing fish swims to and from the surface, and the increased drag when the surface is breached, it can be proposed that air-breathing results in a rise in the apparent cost of transport. In order to investigate this hypothesis, it is necessary to use a fish that is able to swim equally well with and without access to air. The striped catfish Pangasianodon hypophthalmus has been shown to have a sufficiently high capacity for aquatic oxygen uptake in normoxia, to allow for such a comparison. Here, we measured the partitioning of oxygen uptake ( $ \dot{M}{\text{O}}_{2} $ ) during swimming and recovery, and calculated the apparent cost of transport with and without access to air, under normoxic conditions. Aerial $ \dot{M}{\text{O}}_{2} $ constituted 25–40 % of the total $ \dot{M}{\text{O}}_{2} $ during swimming and less than 15 % during recovery. The net cost of transport was 25 % lower in fish that did not air-breathe compared to fish that did, showing that the cost of surfacing can be substantial. This is the first study to measure partitioning in an air-breathing fish during swimming at velocities close to the critical swimming speed. 相似文献
196.
[目的]为了确定铜绿假单胞菌调控因子Pip对两个不同吩嗪合成基因簇(phz1和phz2)的具体调控方式与可能的调控机制.[方法]根据基因比对结果,采用同源重组技术构建Pip调控因子缺失突变株PA-PG以及克隆ip基因作互补分析;再以已构建的吩嗪基因簇缺失突变株PA-Z1G和PA-Z2K为受体菌,构建突变株PA-PD-Z1G和PA-PG-Z2K,测定并比较野生株及相关突变株的吩嗪-1-羧酸和绿脓菌素的合成量,推定Pip对两个不同吩嗪合成基因簇的调控方式.[结果]在GA培养基中,突变株PA-PG的吩嗪-1-羧酸和绿脓菌素都比野生型明显减少;互补分析显示,突变株PA-PG的吩嗪-1-羧酸和绿脓菌素都显著提高并恢复到野生株PAO1水平;突变株PA-Z1G的吩嗪-1-羧酸和绿脓菌素合成量因Pip缺失而显著减少;而突变株PA-Z2K的吩嗪-1-羧酸和绿脓菌素合成量在Pip缺失后仍保持不变.[结论]初步推定,转录调控因子Pip对铜绿假单胞菌吩嗪合成代谢的确具有促进作用;Pip通过正向调控吩嗪基因簇phz2的合成功能实现对吩嗪合成代谢的调控. 相似文献
197.
Keun Sik Baik Yeoung Min Hwang Jong-Soon Choi Joseph Kwon Chi Nam Seong 《Antonie van Leeuwenhoek》2013,104(6):1143-1150
A motile, curved to twisted rod-shaped aerobic bacterium, designated strain 04SU4-PT, was isolated from freshwater collected from the Woopo wetland (Republic of Korea). Cells were observed to be Gram-stain negative, catalase negative and oxidase positive. The major fatty acids (>10 % of the total) were identified as C19:0 ω8c cyclo (24.6 %), C16:0 (24.3 %) and C18:1 ω7c (13.1 %). The DNA G+C content was determined to be 71.5 mol%. The major polar lipids were identified as phosphatidylglycerol, phosphatidylethanolamine, one unknown phospholipid and one unknown aminolipid. The major ubiquinone was determined to be Q-10. A phylogenetic tree based on 16S rRNA gene sequences showed that strain 04SU4-PT forms an evolutionary lineage within the genus Dongia and its nearest neighbour is Dongia mobilis LM22T (98.0 % sequence similarity). Genomic DNA–DNA hybridization of stain 04SU4-PT with D. mobilis LM22T showed relatedness of only 34.2 %. The phenotypic characteristics indicate the strain 04SU4-PT can be distinguished from the sole member of the genus Dongia. On the basis of the data presented in this study, strain 04SU4-PT represents a novel species, for which the name Dongia rigui is proposed. The type strain is 04SU4-PT (KCTC 23341T = JCM 17521T). 相似文献
198.
Sheila Unger Maria?W. Górna Antony Le?Béchec Sonia Do?Vale-Pereira Maria?Francesca Bedeschi Stefan Geiberger Giedre Grigelioniene Eva Horemuzova Faustina Lalatta Ekkehart Lausch Cinzia Magnani Sheela Nampoothiri Gen Nishimura Duccio Petrella Francisca Rojas-Ringeling Akari Utsunomiya Bernhard Zabel Sylvain Pradervand Keith Harshman Belinda Campos-Xavier Luisa Bonafé Giulio Superti-Furga Brian Stevenson Andrea Superti-Furga 《American journal of human genetics》2013,92(6):990-995
Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth. 相似文献
199.
Seo Young Bang Jeong Hoon Kim Phil Young Lee Seung-Wook Chi Sayeon Cho Gwan-Su Yi Pyung Keun Myung Byoung Chul Park Kwang-Hee Bae Sung Goo Park 《Folia microbiologica》2013,58(5):403-408
In Saccharomyces cerevisiae, the Yap family of basic leucine zipper (bZip) proteins contains eight members. The Yap family proteins are implicated in a variety of stress responses; among these proteins, Yap1 acts as a major regulator of oxidative stress responses. However, the functional roles of the remaining Yap family members are poorly understood. To elucidate the function of Yap2, we mined candidate target genes of Yap2 by proteomic analysis. Among the identified genes, FRM2 was previously identified as a target gene of Yap2, which confirmed the validity of our screening method. YNL134C and YDL124W were also identified as candidate Yap2 target genes. These genes were upregulated in strains overexpressing Yap2 and possess Yap2 target sequences in their promoter regions. Furthermore, chromatin immunoprecipitation assays showed that YNL134C and YDL124W have Yap2 binding motif. These data will help to elucidate the functional role of Yap2. 相似文献
200.
Andrew S. Rosenthal Thomas S. Dexheimer Opher Gileadi Giang H. Nguyen Wai Kit Chu Ian D. Hickson Ajit Jadhav Anton Simeonov David J. Maloney 《Bioorganic & medicinal chemistry letters》2013,23(20):5660-5666
Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chemistry optimization of the hit molecule following a quantitative high-throughput screen of >355,000 compounds. These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome. 相似文献