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  1. Article: Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate

    Hancock, Chad N / James M. Phang / W. Gregory Alvord / Wei Liu

    Amino acids. 2016 Mar., v. 48, no. 3

    2016  

    Abstract: Proline dehydrogenase/oxidase (PRODH/POX) is a mitochondrial protein critical to multiple stress pathways. Because of the roles of PRODH/POX in signaling, and its shared localization to the mitochondrial inner membrane with the electron transport chain ( ... ...

    Abstract Proline dehydrogenase/oxidase (PRODH/POX) is a mitochondrial protein critical to multiple stress pathways. Because of the roles of PRODH/POX in signaling, and its shared localization to the mitochondrial inner membrane with the electron transport chain (ETC), we investigated whether there was a direct relationship between PRODH/POX and regulation of the ETC. We found that PRODH/POX binds directly to CoQ1 and that CoQ1-dependent PRODH/POX activity required functional Complex III and Complex IV. PRODH/POX supported respiration in living cells during nutrient stress; however, expression of PRODH/POX resulted in an overall decrease in respiratory fitness. Effects on respiratory fitness were inhibited by DHP and NAC, indicating that these effects were mediated by PRODH/POX-dependent reactive oxygen species (ROS) generation. PRODH/POX expression resulted in a dose-dependent down-regulation of Complexes I–IV of the ETC, and this effect was also mitigated by the addition of DHP and NAC. We found that succinate was an uncompetitive inhibitor of PRODH/POX activity, inhibited ROS generation by PRODH/POX, and alleviated PRODH/POX effects on respiratory fitness. The findings demonstrate novel cross-talk between proline and succinate respiration in vivo and provide mechanistic insights into observations from previous animal studies. Our results suggest a potential regulatory loop between PRODH/POX and succinate in regulation of mitochondrial respiration.
    Keywords animals ; dose response ; electron transport chain ; mitochondrial membrane ; proline ; reactive oxygen species ; succinic acid
    Language English
    Dates of publication 2016-03
    Size p. 859-872.
    Publishing place Springer Vienna
    Document type Article
    ZDB-ID 1121341-3
    ISSN 1438-2199 ; 0939-4451
    ISSN (online) 1438-2199
    ISSN 0939-4451
    DOI 10.1007/s00726-015-2134-7
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: An intergenic non-coding rRNA correlated with expression of the rRNA and frequency of an rRNA single nucleotide polymorphism in lung cancer cells.

    Yih-Horng Shiao / Sorin T Lupascu / Yuhan D Gu / Wojciech Kasprzak / Christopher J Hwang / Janet R Fields / Robert M Leighty / Octavio Quiñones / Bruce A Shapiro / W Gregory Alvord / Lucy M Anderson

    PLoS ONE, Vol 4, Iss 10, p e

    2009  Volume 7505

    Abstract: Ribosomal RNA (rRNA) is a central regulator of cell growth and may control cancer development. A cis noncoding rRNA (nc-rRNA) upstream from the 45S rRNA transcription start site has recently been implicated in control of rRNA transcription in mouse ... ...

    Abstract Ribosomal RNA (rRNA) is a central regulator of cell growth and may control cancer development. A cis noncoding rRNA (nc-rRNA) upstream from the 45S rRNA transcription start site has recently been implicated in control of rRNA transcription in mouse fibroblasts. We investigated whether a similar nc-rRNA might be expressed in human cancer epithelial cells, and related to any genomic characteristics.Using quantitative rRNA measurement, we demonstrated that a nc-rRNA is transcribed in human lung epithelial and lung cancer cells, starting from approximately -1000 nucleotides upstream of the rRNA transcription start site (+1) and extending at least to +203. This nc-rRNA was significantly more abundant in the majority of lung cancer cell lines, relative to a nontransformed lung epithelial cell line. Its abundance correlated negatively with total 45S rRNA in 12 of 13 cell lines (P = 0.014). During sequence analysis from -388 to +306, we observed diverse, frequent intercopy single nucleotide polymorphisms (SNPs) in rRNA, with a frequency greater than predicted by chance at 12 sites. A SNP at +139 (U/C) in the 5' leader sequence varied among the cell lines and correlated negatively with level of the nc-rRNA (P = 0.014). Modelling of the secondary structure of the rRNA 5'-leader sequence indicated a small increase in structural stability due to the +139 U/C SNP and a minor shift in local configuration occurrences.The results demonstrate occurrence of a sense nc-rRNA in human lung epithelial and cancer cells, and imply a role in regulation of the rRNA gene, which may be affected by a +139 SNP in the 5' leader sequence of the primary rRNA transcript.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2009-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Ontogeny-driven rDNA rearrangement, methylation, and transcription, and paternal influence.

    Yih-Horng Shiao / Robert M Leighty / Cuiju Wang / Xin Ge / Erik B Crawford / Joshua M Spurrier / Sean D McCann / Janet R Fields / Laura Fornwald / Lisa Riffle / Craig Driver / Octavio A Quiñones / Ralph E Wilson / Kazimierz S Kasprzak / Gregory S Travlos / W Gregory Alvord / Lucy M Anderson

    PLoS ONE, Vol 6, Iss 7, p e

    2011  Volume 22266

    Abstract: Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and ... ...

    Abstract Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and its subsequent epigenetic modifications may also take place during mammalian ontogeny, a process undergoing finely orchestrated cell division and differentiation. We tested this hypothesis by comparing single nucleotide polymorphism-defined haplotype frequencies and DNA methylation of the rDNA multicopy gene between two mouse ontogenic stages and among three adult tissues of individual mice. Possible influences to the genetic and epigenetic dynamics by paternal exposures were also examined for Cr(III) and acid saline extrinsic factors. Variables derived from litters, individuals, and duplicate assays in large mouse populations were examined using linear mixed-effects model. We report here that active rDNA rearrangement, represented by changes of haplotype frequencies, arises during ontogenic progression from day 8 embryos to 6-week adult mice as well as in different tissue lineages and is modifiable by paternal exposures. The rDNA methylation levels were also altered in concordance with this ontogenic progression and were associated with rDNA haplotypes. Sperm showed highest level of methylation, followed by lungs and livers, and preferentially selected haplotypes that are positively associated with methylation. Livers, maintaining lower levels of rDNA methylation compared with lungs, expressed more rRNA transcript. In vitro transcription demonstrated haplotype-dependent rRNA expression. Thus, the genome is also dynamic during mammalian ontogeny and its rearrangement may trigger epigenetic changes and subsequent transcriptional controls, that are further influenced by paternal exposures.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists

    Wei Huang, Da / Brad T Sherman / H Clifford Lane / Jack R Collins / Jean Roayaei / Michael W Baseler / Qina Tan / Richard A Lempicki / Robert Stephens / W Gregory Alvord

    Genome biology. 2007 Sept., v. 8, no. 9

    2007  

    Abstract: The DAVID Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. ... ...

    Abstract The DAVID Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context.
    Keywords algorithms ; bioinformatics ; genes ; molecular genetics
    Language English
    Dates of publication 2007-09
    Size p. 1664.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2007-8-9-r183
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Serum S100A6 concentration predicts peritoneal tumor burden in mice with epithelial ovarian cancer and is associated with advanced stage in patients.

    Bih-Rong Wei / Shelley B Hoover / Mark M Ross / Weidong Zhou / Francesco Meani / Jennifer B Edwards / Elizabeth I Spehalski / John I Risinger / W Gregory Alvord / Octavio A Quiñones / Claudio Belluco / Luca Martella / Elio Campagnutta / Antonella Ravaggi / Ren-Ming Dai / Paul K Goldsmith / Kevin D Woolard / Sergio Pecorelli / Lance A Liotta /
    Emanuel F Petricoin / R Mark Simpson

    PLoS ONE, Vol 4, Iss 10, p e

    2009  Volume 7670

    Abstract: BACKGROUND:Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved ... ...

    Abstract BACKGROUND:Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS:Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS:S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 616 ; 610
    Language English
    Publishing date 2009-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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