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981.
Elena Favaro Anassuya Ramachandran Robert McCormick Harriet Gee Christine Blancher Meredith Crosby Cecilia Devlin Christopher Blick Francesca Buffa Ji-Liang Li Borivoj Vojnovic Ricardo Pires das Neves Peter Glazer Francisco Iborra Mircea Ivan Jiannis Ragoussis Adrian L. Harris 《PloS one》2010,5(4)
Background
Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis.Methods and Findings
In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis.Conclusions
Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation. 相似文献982.
Ariel M. Pani Holly H. Hobart Colleen A. Morris Carolyn B. Mervis Patricia Bray-Ward Kendra W. Kimberley Cecilia M. Rios Robin C. Clark Maricela D. Gulbronson Gordon C. Gowans Ronald G. Gregg 《PloS one》2010,5(8)
Background
Intellectual disability (ID) affects 2–3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for ∼50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.Methodology/Principal Findings
High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Conclusions/Significance
Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information. 相似文献983.
Functional characterization of muscle fibers relies on ATPase activity and on differential measurements of metabolic proteins, including mitochondrial and glycolytic enzymes, glucose, lactate and lactic acid transporters, calcium cycling proteins and components of the contractile machinery. The recent introduction of microarray technology has enabled detailed gene expression studies under different physiological and pathological conditions, thus generating novel hypotheses on muscle function. However, microarray approaches are limited by the incomplete genome coverage of currently available chips, and by poor correlation between mRNA concentration and protein expression level. We have used 2-DE and MS to build a reference map of proteins from rat mixed gastrocnemius and soleus muscle, and to assess qualitative and quantitative differences in protein distribution between these two functionally dissimilar muscles. More than 800 spots on each gel were detected by silver staining, of which 167 were excised, digested in-gel with trypsin and analyzed by ESI-MS/MS. One hundred and twenty eight distinct gene products were identified, including metabolic, transport and contractile proteins. Forty one spots displayed differences in relative expression level between mixed gastrocnemius and soleus samples. These data not only enable differentiation of functionally distinct slow-twitch and fast-twitch fiber types, but also provide tools for investigating muscle plasticity in response to physiological and environmental conditions such as aging or hypoxia. 相似文献
984.
D'Elia D Catalano D Licciulli F Turi A Tripoli G Porcelli D Saccone C Caggese C 《Mitochondrion》2006,6(5):252-257
The oxidative phosphorylation (OXPHOS) is the primary energy-producing process of all aerobic organisms and the only cellular function under the dual control of both the mitochondrial and the nuclear genomes. Functional characterization and evolutionary study of the OXPHOS system is of great importance for the understanding of many as yet unclear aspects of nucleus-mitochondrion genomic co-evolution and co-regulation gene networks. The MitoDrome database is a web-based database which provides genomic annotations about nuclear genes of Drosophila melanogaster encoding for mitochondrial proteins. Recently, MitoDrome has included a new section annotating genomic information about OXPHOS genes in Drosophila pseudoobscura and Anopheles gambiae and their comparative analysis with their Drosophila melanogaster and human counterparts. The introduction of this new comparative annotation section into MitoDrome is expected to be a useful resource for both functional and structural genomics related to the OXPHOS system. 相似文献
985.
Hjernø K Alm R Canbäck B Matthiesen R Trajkovski K Björk L Roepstorff P Emanuelsson C 《Proteomics》2006,6(5):1574-1587
Proteomic screening of strawberry (Fragaria ananassa) yielded a 58% success rate in protein identification in spite of the fact that no genomic sequence is available for this species. This was achieved by a combination of MALDI-MS/MS de novo sequencing of double-derivatized peptides and indel-tolerant searching against local protein databases built on both EST and full-length nucleotide sequences. The amino acid sequence of a strawberry allergen, homologous to the well-known major birch pollen allergen Bet v 1, was partially determined. This strawberry allergen, named Fra a 1 according to the nomenclature for allergen proteins, showed sequence identity of 54 and 77%, respectively, with corresponding allergens from birch and apple. Differential expression, as evaluated by 2-D DIGE, occurred in 10% of protein spots when red strawberries were compared to a colorless (white) strawberry mutant. White strawberries, known to be tolerated by individuals affected by allergy, were found to be virtually free from the strawberry allergen. Also several enzymes in the pathway for biosynthesis of flavonoids, to which the red color pelargonidin belongs, were down-regulated. This approach to assess differential protein expression without access to genomic sequence information can also be applied to other crop plants and phenotypic traits. 相似文献
986.
987.
Bhaswati Guha Colin D. Hills Paula J. Carey Cecilia L. MacLeod 《Soil & Sediment Contamination》2006,15(6):621-635
This study investigated traditional cement-based and non-conventional (using accelerated carbonation) solidification/stabilization to treat 2 dredged sediments contaminated with mercury from two different locations in UK. Canal and estuarine-derived sediments were mixed with blended binders and powdered activated carbon. Fresh mixtures of sediment and cement were exposed to gaseous carbon dioxide and were allowed to carbonate for fixed time periods, after which they were cured for 28 days. Following curing, samples were leach tested to evaluate the fixation of mercury in the treated products. The results obtained indicated that both conventional and accelerated carbonated treatments were capable of reducing the concentration of mercury in the eluates to acceptable limits. 相似文献
988.
989.
Nucleotide Substitution Rate of Mammalian Mitochondrial Genomes 总被引:22,自引:0,他引:22
We present here for the first time a comprehensive study based on the analysis of closely related organisms to provide an
accurate determination of the nucleotide substitution rate in mammalian mitochondrial genomes. This study examines the evolutionary
pattern of the different functional mtDNA regions as accurately as possible on the grounds of available data, revealing some
important ``genomic laws.' The main conclusions can be summarized as follows. (1) High intragenomic variability in the evolutionary
dynamic of mtDNA was found. The substitution rate is strongly dependent on the region considered, and slow- and fast-evolving
regions can be identified. Nonsynonymous sites, the D-loop central domain, and tRNA and rRNA genes evolve much more slowly
than synonymous sites and the two peripheral D-loop region domains. The synonymous rate is fairly uniform over the genome,
whereas the rate of nonsynonymous sites depends on functional constraints and therefore differs considerably between genes.
(2) The commonly accepted statement that mtDNA evolves more rapidly than nuclear DNA is valid only for some regions, thus
it should be referred to specific mitochondrial components. In particular, nonsynonymous sites show comparable rates in mitochondrial
and nuclear genes; synonymous sites and small rRNA evolve about 20 times more rapidly and tRNAs about 100 times more rapidly
in mitochondria than in their nuclear counterpart. (3) A species-specific evolution is particularly evident in the D-loop
region. As the divergence times of the organism pairs under consideration are known with sufficient accuracy, absolute nucleotide
substitution rates are also provided.
Received: 11 May 1998 / Accepted: 2 September 1998 相似文献
990.
PKC-epsilon regulates basolateral endocytosis in human T84 intestinal epithelia: role of F-actin and MARCKS 总被引:2,自引:0,他引:2
Song Jaekyung Cecilia; Hrnjez Bruce J.; Farokhzad Omid C.; Matthews Jeffrey B. 《American journal of physiology. Cell physiology》1999,277(6):C1239
Protein kinase C (PKC) and the actin cytoskeleton are criticaleffectors of membrane trafficking in mammalian cells. In polarized epithelia, the role of these factors in endocytic events at either theapical or basolateral membrane is poorly defined. In the present study,phorbol 12-myristate 13-acetate (PMA) and other activators of PKCselectively enhanced basolateral but not apical fluid-phase endocytosisin human T84 intestinal epithelia. Stimulation of basolateralendocytosis was blocked by the conventional and novel PKC inhibitorGö-6850, but not the conventional PKC inhibitor Gö-6976,and correlated with translocation of the novel PKC isoform PKC-. PMAtreatment induced remodeling of basolateral F-actin. The actindisassembler cytochalasin D stimulated basolateral endocytosis andenhanced stimulation of endocytosis by PMA, whereas PMA-stimulated endocytosis was blocked by the F-actin stabilizers phalloidin andjasplakinolide. PMA induced membrane-to-cytosol redistribution of theF-actin cross-linking protein myristoylated alanine-rich C kinasesubstrate (MARCKS). Cytochalasin D also induced MARCKS translocationand enhanced PMA-stimulated translocation of MARCKS. A myristoylatedpeptide corresponding to the phosphorylation site domain of MARCKSinhibited both MARCKS translocation and PMA stimulation of endocytosis.MARCKS translocation was inhibited by Gö-6850 but notGö-6976. The results suggest that a novel PKC isoform, likelyPKC-, stimulates basolateral endocytosis in model epithelia by amechanism that involves F-actin and MARCKS. 相似文献