Mitochondrial-Dna and Nuclear-Gene Differentiation in North American Prairie Grouse (Genus Tympanuchus)

Total Page:16

File Type:pdf, Size:1020Kb

Mitochondrial-Dna and Nuclear-Gene Differentiation in North American Prairie Grouse (Genus Tympanuchus) The Auk 111(3):661-671, 1994 MITOCHONDRIAL-DNA AND NUCLEAR-GENE DIFFERENTIATION IN NORTH AMERICAN PRAIRIE GROUSE (GENUS TYMPANUCHUS) DARRELL L. ELLSWORTH,L3 RODNEY L. HONEYCUTT, i NOVA J. SILVY,• KEVIN D. RITTENHOUSE,x AND MICHAEL H. SMITH 2 •WildlifeGenetics Laboratory, Department of Wildlifeand Fisheries Sciences, TexasA&M University,College Station, Texas 77843, USA; and 2SavannahRiver Ecology Laboratory, P.O. DrawerE, Aiken,South Carolina 29801, USA ABSTP,•CT.--Thefragmentary effects of Pleistoceneglacial activity have been implicated in speciation among avifauna endemic to the Central Plains of North America. The prairie- grousecomplex (genus Tympanuchus),distributed throughout the central United Statesand Canada,contains three sistertaxa believed to have originated from the expansionof late Pleistocenerefugial populations.We assayedmitochondrial-DNA (mtDNA) restriction-site and allozyme variation in prairie grouseobtained from localitiesthroughout their current range in North Americato examinethe nature and timing of eventspromoting differentiation in Tympanuchus.The geneticdata were not consistentwith Pleistoceneisolation of sufficient duration to allow a taxonomicallyor geographicallystructured pattern of genetic variation to emerge. No clear genetic differencesamong specieswere observed.Allozymes could not distinguishpopulations belonging to different speciesand frequencieswere generally similar acrosstaxa. The mtDNA differentiationwas characterizedby a predominanthaplotype shared by all taxa;the remainder(15) were generallyinfrequent and closelyrelated to the prevalent (and presumablyancestral) haplotype. The presenceof unique mtDNA haplotypeswithin speciesand absenceof certain allozyme alleles from particular taxa implied a degree of isolation and restrictionsto gene flow. However, the mtDNA haplotypesdid not sort phy- logenetically,which suggestsrecent commonancestry of the lineagesand may explain the lack of congruencebetween genetic variation and speciesdesignations. Despite the absence of quantitativegenetic differentiation, considerable morphological and behavioraldifferences are apparent among the putative species.Adult male plumage, vocalization structures,and courtshipbehaviors form the basisfor taxonomicdivisions among prairie grouse,but, con- sidering their closeassociation with reproduction,such charactersmay be subjectto sexual selectionand may evolve rapidly relative to mtDNA or allozymes. Received27 January1993, accepted19 August1993. RANGE FRAGMENTATION and isolation associ- Many subspeciesand speciesin the Great Plains ated with Pleistocene glaciation have been are assumedto have arisen through geographic widely implicated in the differentiation of var- isolationin refugia during Pleistoceneglacial iousclosely related, but largely allopatric,avian maxima (Selander 1965, Hubbard 1973). Con- species(Rand 1948, Mengel 1964, 1970, Selan- versely,the low speciesdiversity of grassland der 1965). The Central Plains of North America, birds and paucity of closely related congeners in particular,have been viewed as an isolating led Mengel (1970) to hypothesizethat there has agent promoting speciation among avian taxa been little pastfractionation of the Central Plains that now occupyeastern deciduous and western into isolated environments. Therefore, it is un- montane forest (Mengel 1964, 1970, Berming- clear as to whether differentiation and specia- ham et al. 1992). However, the role of glacial tion amongbirds of the Central Plains may be activity in the speciationof avifauna endemic attributedto allopatric(due to isolation)or sym- to the Central Plains is not well understood. patric (without geographicsubdivision) mech- anisms. 3 Present address: Center for Demographic and The prairie grouse(genus Tympanuchus) com- Population Genetics,University of TexasHealth Sci- prise an interesting "speciescomplex" for ex- ence Center at Houston, P.O. Box 20334, Houston, amining the competing hypothesesregarding Texas 77225, USA. the fate of the Central Plains during the Pieis- 661 662 ELLSWORTHETAL. [Auk,Vol. 111 tocene and possible modes of differentiation/ gent avian sister taxa believed to have origi- speciationamong birds of the North American nated from the expansion of late Pleistocene grasslands.The prairie-grouse complex con- refugial populations.In this study,we assessed tains three primarily grasslandadapted sister mtDNA andallozyme variation in prairiegrouse taxa distributedthroughout the central United and testedprevious hypotheses regarding dif- Statesand Canada.Two extant formsof T. cupido ferentiation and speciation among the taxa. (Greater Prairie-Chicken) occur primarily in Specifically,we addressedthe following ques- remnant tall-grassprairie in Kansas,Nebraska, tions:What is the nature of genetic differenti- Oklahoma,and SouthDakota (T. c.pinnatus) and ation in the prairie-grouse complex?Are the in smallendangered populations along the Tex- patternsof geneticvariation and estimatedtimes as Gulf Coast (T. c. attwateri; Westemeier 1980). sincedivergence among mtDNA lineagescon- Tympanuchuspallidicinctus (Lesser Prairie-Chick- sistent with late Pleistocene (recent) vicarlance? en) occupies the shrub grasslandsof south- Has sporadic interspecific hybridization in- western Kansassouthward through Oklahoma ducedby human activity influencedthe pattern to eastern New Mexico (Waddell and Hanzlick of differentiationamong taxa?How do levels 1978, Cannon and Knopf 1980, Taylor and of genetic differentiation comparewith mor- Guthery 1980), and T. phasianellus(Sharp-tailed phologicaland behavioraldivergence among Grouse) is resident to the north-central United the putative species? States and central Canada to Alaska (Miller and Graul 1980). METHODS Tympanuchuscupido and T. pallidicinctusare recognized as distinct species(AOU 1983) due Specirnens.--Tissues(brain, heart, liver) were ob- to differences in behavior, habitat affiliation, tained from 86 prairie grouseand frozen on dry ice. and socialaggregation (Grange 1940, Jones 1964, Most birds were harvestedby hunters, but samples Sharpe 1968). However, the differencesare not from the endangered T. c. attwateriwere taken from asgreat asthose seen among other well-defined incidental mortalities at the Attwater Prairie-Chicken grousespecies, causing some researchers (Short National Wildlife Refuge. Collection sites, listed be- 1967, Johnsgard1983) to regard these taxa as low by state and county (USA) or province and mu- nicipality (Canada),were locatedthroughout the cur- allopatricsubspecies. Conversely, T. phasianellus rent range of each taxon: T. c. pinnatus,ILLINOIS, is morphologicallydistinct from the "prairie Jasper(2), Marion (2), KANSAS, Butler (3), Chase(5), chickens." Elongated central and reduced pe- Lyon (2), Shawnee (4), NEBRASKA, Rock (3), Thomas ripheral rectricesas well asrudimentary pinnae (3), OKLAHOMA, Osage(3), SOUTH DAKOTA, Ly- and cervicalapteria distinguish phasianellus from man (6); T. c. attwateri,TEXAS, Colorado(1), Refugio cupidoand pallidicinctus(Ridgway and Fried- (1); T. pallidicinctus,KANSAS, Clark (9), Morton (7); mann 1946). In fact, phasianellus(formerly Pe- T. phasianellus,COLORADO, Routt (2), MANITOBA, dioecetesphasianellus) was once placed in a dis- CANADA, Coldwell (4), Chetfield (2), MINNESOTA, tinct monotypicgenus, but Pedioeceteshas been Aitkin (4), Lake of the Woods (3), NEBRASKA, Tho- synonymized with Tympanuchusto reflect phys- mas(5), Rock (1), NORTH DAKOTA, Billings (1), Bur- leigh (1), Grant (2), McKenzie (1), Morton (1), SOUTH iological (Hudson et al. 1959, 1966) and de- DAKOTA, Campbell (1), Dewey (2), Lyman (2), QUE- mographicsimilarities. BEC,CANADA, Ungava Comt• (3). Wisconsinglaciation has been cited as the Mitochondrial-DNA analysis.--In the laboratory, primary factor promoting subdivisionand di- mtDNA was isolated from frozen tissueand purified vergence among prairie-grouse populations. on cesiumchloride density gradients(Cart and Grif- Hubbard(1973) hypothesized that prairiegrouse fith 1987).Mitochondrial DNA from 51 prairie grouse were continuouslydistributed throughout much (T. c. pinnatus,21; T. c. attwateri,2; T. pallidicinctus,6; of the Great Plains during the Sangamon in- T. phasianellus,22) representativeof localitiesfrom the terglacial,but that considerablerange fragmen- Texas Gulf Coast to Hudson Bay was digested with tation and isolation of populations occurred 12 six-base-recognizing(Barnil I, Cla I, Dra I, EcoRI, EcoRV, Hind III, Nde I, Pst I, SspI, SstI, Stu I, Xba I) during the Wisconsinglacial period. Differen- and 4 four-base-recognizing(Hha I, Msp I, RsaI, Taq tiation within isolated refugia and postglacial I) restriction enzymes. Fragmentswere end-labeled reinvasion of the plains may thus have pro- with 32P-deoxynucleotides,separated by molecular duced the distribution of extant taxa. Therefore, weight on 1.2% agaroseor 4% acrylamide gels, and prairie grouseare useful for characterizingge- visualizedby autoradiography.Fragment sizes were netic variation among morphologicallydiver- estimatedfrom comigrating molecular size standards July1994] DifferentiationinPrairie Grouse 663 composedof lambda DNA and PM2 DNA digested phate dehydrogenase(L) (GAPD; 1.2.1.12);aglycerol- with Hind III. 3-phosphate dehydrogenase (L) (GPD1; 1.1.1.8); Unique fragment patterns produced by each re- sorbitoldehydrogenase (L) (SORD;1.1.1.14); and xan- striction enzyme were designatedalphabetically in thine dehydrogenase(L) (XDH; 1.1.1.204).(2) Con- chronologicalorder of discovery.Restriction sites were tinuous tris
Recommended publications
  • Mt-Atp8 Gene in the Conplastic Mouse Strain C57BL/6J-Mtfvb/NJ on the Mitochondrial Function and Consequent Alterations to Metabolic and Immunological Phenotypes
    From the Lübeck Institute of Experimental Dermatology of the University of Lübeck Director: Prof. Dr. Saleh M. Ibrahim Interplay of mtDNA, metabolism and microbiota in the pathogenesis of AIBD Dissertation for Fulfillment of Requirements for the Doctoral Degree of the University of Lübeck from the Department of Natural Sciences Submitted by Paul Schilf from Rostock Lübeck, 2016 First referee: Prof. Dr. Saleh M. Ibrahim Second referee: Prof. Dr. Stephan Anemüller Chairman: Prof. Dr. Rainer Duden Date of oral examination: 30.03.2017 Approved for printing: Lübeck, 06.04.2017 Ich versichere, dass ich die Dissertation ohne fremde Hilfe angefertigt und keine anderen als die angegebenen Hilfsmittel verwendet habe. Weder vorher noch gleichzeitig habe ich andernorts einen Zulassungsantrag gestellt oder diese Dissertation vorgelegt. ABSTRACT Mitochondria are critical in the regulation of cellular metabolism and influence signaling processes and inflammatory responses. Mitochondrial DNA mutations and mitochondrial dysfunction are known to cause a wide range of pathological conditions and are associated with various immune diseases. The findings in this work describe the effect of a mutation in the mitochondrially encoded mt-Atp8 gene in the conplastic mouse strain C57BL/6J-mtFVB/NJ on the mitochondrial function and consequent alterations to metabolic and immunological phenotypes. This work provides insights into the mutation-induced cellular adaptations that influence the inflammatory milieu and shape pathological processes, in particular focusing on autoimmune bullous diseases, which have recently been reported to be associated with mtDNA polymorphisms in the human MT-ATP8 gene. The mt-Atp8 mutation diminishes the assembly of the ATP synthase complex into multimers and decreases mitochondrial respiration, affects generation of reactive oxygen species thus leading to a shift in the metabolic balance and reduction in the energy state of the cell as indicated by the ratio ATP to ADP.
    [Show full text]
  • Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REPORT Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ Ortal Barel,1 Zamir Shorer,2 Hagit Flusser,2 Rivka Ofir,1 Ginat Narkis,1 Gal Finer,1 Hanah Shalev,2 Ahmad Nasasra,2 Ann Saada,3 and Ohad S. Birk1,4,* A consanguineous Israeli Bedouin kindred presented with an autosomal-recessive nonlethal phenotype of severe psychomotor retarda- tion and extrapyramidal signs, dystonia, athetosis and ataxia, mild axial hypotonia, and marked global dementia with defects in verbal and expressive communication skills. Metabolic workup was normal except for mildly elevated blood lactate levels. Brain magnetic resonance imaging (MRI) showed increased density in the putamen, with decreased density and size of the caudate and lentiform nuclei. Reduced activity specifically of mitochondrial complex III and variable decrease in complex I activity were evident in muscle biopsies. Homozygosity of affected individuals to UQCRB and to BCSIL, previously associated with isolated complex III deficiency, was ruled out. Genome-wide linkage analysis identified a homozygosity locus of approximately 9 cM on chromosome 5q31 that was further narrowed down to 2.14 cM, harboring 30 genes (logarithm of the odds [LOD] score 8.82 at q ¼ 0). All 30 genes were sequenced, revealing a single missense (p.Ser45Phe) mutation in UQCRQ (encoding ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5 kDa), one of the ten nuclear
    [Show full text]
  • Biomarkers of Mitotoxicity After Acute Liver Injury: Further Insights Into the Interpretation of Glutamate Dehydrogenase
    Journal of Clinical and Translational Research 10.18053/Jctres/07.202101.005 MINI REVIEW Biomarkers of mitotoxicity after acute liver injury: further insights into the interpretation of glutamate dehydrogenase Mitchell R. McGill1,2* and Hartmut Jaeschke3 1. Department of Environmental Health Sciences, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, 4301 W. Markham St, Little Rock, AR, USA, 72205 2. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR, USA, 72205 3. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, USA, 66160 *Corresponding author Mitchell R. McGill, PhD Department of Environmental Health Sciences & Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR Tel: +1 501-526-6696 Email: [email protected] Article information: Received: November 03, 2020 Revised: December 09, 2020 Accepted: December 10, 2020 Journal of Clinical and Translational Research 10.18053/Jctres/07.202101.005 ABSTRACT Background: Acetaminophen (APAP) is a popular analgesic, but overdose causes acute liver injury and sometimes death. Decades of research have revealed that mitochondrial damage is central in the mechanisms of toxicity in rodents, but we know much less about the role of mitochondria in humans. Due to the challenge of procuring liver tissue from APAP overdose patients, non-invasive mechanistic biomarkers are necessary to translate the mechanisms of APAP hepatotoxicity from rodents to patients. It was recently proposed that the mitochondrial matrix enzyme glutamate dehydrogenase (GLDH) can be measured in circulation as a biomarker of mitochondrial damage.
    [Show full text]
  • Tyramine and Amyloid Beta 42: a Toxic Synergy
    biomedicines Article Tyramine and Amyloid Beta 42: A Toxic Synergy Sudip Dhakal and Ian Macreadie * School of Science, RMIT University, Bundoora, VIC 3083, Australia; [email protected] * Correspondence: [email protected]; Tel.: +61-3-9925-6627 Received: 5 May 2020; Accepted: 27 May 2020; Published: 30 May 2020 Abstract: Implicated in various diseases including Parkinson’s disease, Huntington’s disease, migraines, schizophrenia and increased blood pressure, tyramine plays a crucial role as a neurotransmitter in the synaptic cleft by reducing serotonergic and dopaminergic signaling through a trace amine-associated receptor (TAAR1). There appear to be no studies investigating a connection of tyramine to Alzheimer’s disease. This study aimed to examine whether tyramine could be involved in AD pathology by using Saccharomyces cerevisiae expressing Aβ42. S. cerevisiae cells producing native Aβ42 were treated with different concentrations of tyramine, and the production of reactive oxygen species (ROS) was evaluated using flow cytometric cell analysis. There was dose-dependent ROS generation in wild-type yeast cells with tyramine. In yeast producing Aβ42, ROS levels generated were significantly higher than in controls, suggesting a synergistic toxicity of Aβ42 and tyramine. The addition of exogenous reduced glutathione (GSH) was found to rescue the cells with increased ROS, indicating depletion of intracellular GSH due to tyramine and Aβ42. Additionally, tyramine inhibited the respiratory growth of yeast cells producing GFP-Aβ42, while there was no growth inhibition when cells were producing GFP. Tyramine was also demonstrated to cause increased mitochondrial DNA damage, resulting in the formation of petite mutants that lack respiratory function.
    [Show full text]
  • Clostridium Difficile Exploits a Host Metabolite Produced During Toxin-Mediated Infection
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.14.426744; this version posted January 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Clostridium difficile exploits a host metabolite produced during toxin-mediated infection 2 3 Kali M. Pruss and Justin L. Sonnenburg* 4 5 Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford 6 CA, USA 94305 7 *Corresponding author address: [email protected] 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.14.426744; this version posted January 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 23 Several enteric pathogens can gain specific metabolic advantages over other members of 24 the microbiota by inducing host pathology and inflammation. The pathogen Clostridium 25 difficile (Cd) is responsible for a toxin-mediated colitis that causes 15,000 deaths in the U.S. 26 yearly1, yet the molecular mechanisms by which Cd benefits from toxin-induced colitis 27 remain understudied. Up to 21% of healthy adults are asymptomatic carriers of toxigenic 28 Cd2, indicating that Cd can persist as part of a healthy microbiota; antibiotic-induced 29 perturbation of the gut ecosystem is associated with transition to toxin-mediated disease.
    [Show full text]
  • Ular Basis of KAISER, S
    Heredity 74 (1995) 267—273 Received6May 1994 OThe Genetical Society of Great Britain 1981. The molecular basis of KAISER, S. 1935. The factorsSOMMER, controlling H. 1991. Genetic shape control ofand flower sizedevelopment in Genetic differentiation among populations of by homeotic genes in Antirrhinum majus. Science, 250, Myopus schisticolor (the wood lemming) — LANDE, R. 1981. The minimumSHORE, number J. S. AND BARRETF, of genes S. C. H. 1990. contributing Quantitative genetics of floral characters in homostylous Turnera ulmifolia var, isozyme variation angustifolia Willd. (Turneraceae). Heredity, 64, LANDE, R, 1983. The responseSINNO1F, to e. w.selection 1935. Evidence onfor the major existence of and genes VADIM B. FEDOROVif, RICKARD FREDRIKSSON1: & KARLFREDGA* SINNO'rr, E. w. 1936. A developmental analysis of inherited t/nstitute of Plant and Animal Ecology, Russian Academy of Sciences, 8 March Street 202, Jekaterinburg 620 008, tion on correlated characters.shape Evolution, differences in Cucurbit37, 1210—1226. fruits. Am. Nat., 70, Russia and Department of Genetics, Uppsa/a University, Box 7003, S-75007Uppsala, Sweden LORD, C. M. AND HILL, .i. i'. 1987. Evidence for heterochrony in Toinvestigate genetic differentiation among populations of the wood lemming Myopus schistico!or (eds) Development as an Evolutiona,ySMITH, H. H. 1950. DevelopmentalProcess, restrictions pp. 47—70. on recombina- (Muridae, Rodentia) isozyme variation in 10 populations from three regions, Fennoscandia, Western and Eastern Siberia, was examined. From 20 loci examined, the two most polymorphic MACNAIR, M. R. AND CUMBES,TAKHTAJAN, o. .i. 1989. A. 1976. The Neoteny genetic and the architectureorigin of flowering ones, Idh-1 and Pgi-1, were used in the complete survey.
    [Show full text]
  • Protection Against Apoptosis by Monoamine Oxidase a Inhibitors
    View metadata,FEBS 20082 citation and similar papers at core.ac.uk FEBS Letters 426 (1998)brought to 155^159 you by CORE provided by Elsevier - Publisher Connector Protection against apoptosis by monoamine oxidase A inhibitors W. Malornia;*, A.M. Giammariolia, P. Matarresea, P. Pietrangelib, E. Agostinellib, A. Ciacciob, E. Grassillic, B. Mondovi'b aDepartment of Ultrastructures, Istituto Superiore di Sanitaé, Viale Regina Elena 299, 00161 Rome, Italy bDepartment of Biochemical Sciences and CNR Center of Molecular Biology, University of Rome `La Sapienza', Rome, Italy cDepartment of General Pathology, University of Modena, Modena, Italy Received 27 February 1998 mitochondrial membrane potential or apoptosis. Analytical Abstract Several lines of evidence have been accumulating indicating that an important role may be played by mitochondrial cytology analyses revealed that maintenance of the mitochon- homeostasis in the initiation phase, the first stage of apoptosis. drial homeostasis by pargyline and clorgyline is associated This work describes the results obtained by using different with a partial hindering of the apoptotic process. inhibitors of monoamine oxidases (MAO), i.e. pargyline, clorgyline and deprenyl, on mitochondrial integrity and apopto- 2. Materials and methods sis. Both pargyline and clorgyline are capable of protecting cells from apoptosis induced by serum starvation while deprenyl is 2.1. Cell cultures ineffective. These data represent the first demonstration that Human melanoma cells (M14) were grown in monolayer in modi- MAO-A inhibitors may protect cells from apoptosis through a ¢ed RPMI 1640 medium supplemented with 10% heat-inactivated mechanism involving the maintenance of mitochondrial homeo- fetal calf serum (FCS), 1 mM sodium pyruvate, 1% non-essential stasis.
    [Show full text]
  • Regional Differences in Mitochondrial DNA Methylation in Human Post-Mortem Brain Tissue Matthew Devall1, Rebecca G
    Devall et al. Clinical Epigenetics (2017) 9:47 DOI 10.1186/s13148-017-0337-3 SHORT REPORT Open Access Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue Matthew Devall1, Rebecca G. Smith1, Aaron Jeffries1,2, Eilis Hannon1, Matthew N. Davies3, Leonard Schalkwyk4, Jonathan Mill1,2, Michael Weedon1 and Katie Lunnon1* Abstract Background: DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have been limited to the investigation of specific target regions. Analyses spanning the entire mitochondrial genome have been limited, potentially due to the amount of input DNA required. Further, mitochondrial genetic studies have been previously confounded by nuclear-mitochondrial pseudogenes. Methylated DNA Immunoprecipitation Sequencing is a technique widely used to profile DNA methylation across the nuclear genome; however, reads mapped to mitochondrial DNA are often discarded. Here, we have developed an approach to control for nuclear-mitochondrial pseudogenes within Methylated DNA Immunoprecipitation Sequencing data. We highlight the utility of this approach in identifying differences in mitochondrial DNA methylation across regions of the human brain and pre-mortem blood. Results: We were able to correlate mitochondrial DNA methylation patterns between the cortex, cerebellum and blood. We identified 74 nominally significant differentially methylated regions (p < 0.05) in the mitochondrial genome, between anatomically separate cortical regions and the cerebellum in matched samples (N = 3 matched donors). Further analysis identified eight significant differentially methylated regions between the total cortex and cerebellum after correcting for multiple testing.
    [Show full text]
  • Global Profiling of Metabolic Adaptation to Hypoxic Stress in Human Glioblastoma Cells
    Global profiling of metabolic adaptation to hypoxic stress in human glioblastoma cells. Kucharzewska, Paulina; Christianson, Helena; Belting, Mattias Published in: PLoS ONE DOI: 10.1371/journal.pone.0116740 2015 Link to publication Citation for published version (APA): Kucharzewska, P., Christianson, H., & Belting, M. (2015). Global profiling of metabolic adaptation to hypoxic stress in human glioblastoma cells. PLoS ONE, 10(1), [e0116740]. https://doi.org/10.1371/journal.pone.0116740 Total number of authors: 3 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Download date: 07. Oct. 2021 RESEARCH ARTICLE Global Profiling of Metabolic Adaptation to Hypoxic Stress in Human Glioblastoma Cells Paulina Kucharzewska1, Helena C.
    [Show full text]
  • Mitochondrial Dysfunction in Parkinson's Disease: Focus on Mitochondrial
    biomedicines Review Mitochondrial Dysfunction in Parkinson’s Disease: Focus on Mitochondrial DNA Olga Buneeva, Valerii Fedchenko, Arthur Kopylov and Alexei Medvedev * Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, Russia; [email protected] (O.B.); [email protected] (V.F.); [email protected] (A.K.) * Correspondence: [email protected]; Tel.: +7-495-245-0509 Received: 17 November 2020; Accepted: 8 December 2020; Published: 10 December 2020 Abstract: Mitochondria, the energy stations of the cell, are the only extranuclear organelles, containing their own (mitochondrial) DNA (mtDNA) and the protein synthesizing machinery. The location of mtDNA in close proximity to the oxidative phosphorylation system of the inner mitochondrial membrane, the main source of reactive oxygen species (ROS), is an important factor responsible for its much higher mutation rate than nuclear DNA. Being more vulnerable to damage than nuclear DNA, mtDNA accumulates mutations, crucial for the development of mitochondrial dysfunction playing a key role in the pathogenesis of various diseases. Good evidence exists that some mtDNA mutations are associated with increased risk of Parkinson’s disease (PD), the movement disorder resulted from the degenerative loss of dopaminergic neurons of substantia nigra. Although their direct impact on mitochondrial function/dysfunction needs further investigation, results of various studies performed using cells isolated from PD patients or their mitochondria (cybrids) suggest their functional importance. Studies involving mtDNA mutator mice also demonstrated the importance of mtDNA deletions, which could also originate from abnormalities induced by mutations in nuclear encoded proteins needed for mtDNA replication (e.g., polymerase γ). However, proteomic studies revealed only a few mitochondrial proteins encoded by mtDNA which were downregulated in various PD models.
    [Show full text]
  • Polyol Pathway Links Glucose Metabolism to the Aggressiveness
    Published OnlineFirst January 17, 2018; DOI: 10.1158/0008-5472.CAN-17-2834 Cancer Metabolism and Chemical Biology Research Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells Annemarie Schwab1, Aarif Siddiqui1, Maria Eleni Vazakidou1, Francesca Napoli1, Martin Bottcher€ 2, Bianca Menchicchi3, Umar Raza4, Ozge€ Saatci4, Angela M. Krebs5, Fulvia Ferrazzi6, Ida Rapa7, Katja Dettmer-Wilde8, Maximilian J. Waldner3, Arif B. Ekici6, Suhail Ahmed Kabeer Rasheed9, Dimitrios Mougiakakos2, Peter J. Oefner8, Ozgur Sahin4, Marco Volante7, Florian R. Greten10, Thomas Brabletz5, and Paolo Ceppi1 Abstract Cancer cells alter their metabolism to support their malig- sequencing confirmed a profound alteration of EMT in PP- nant properties. In this study, we report that the glucose- deficient cells, revealing a strong repression of TGFb signature transforming polyol pathway (PP) gene aldo-keto-reductase- genes. Excess glucose was found to promote EMT through 1-member-B1 (AKR1B1) strongly correlates with epithelial-to- autocrine TGFb stimulation, while PP-deficient cells were mesenchymal transition (EMT). This association was con- refractory to glucose-induced EMT. These data show that PP firmed in samples from lung cancer patients and from an represents a molecular link between glucose metabolism, can- EMT-driven colon cancer mouse model with p53 deletion. In cer differentiation, and aggressiveness, and may serve as a novel vitro, mesenchymal-like cancer cells showed increased AKR1B1 therapeutic target. levels, and AKR1B1 knockdown was sufficient to revert EMT. An Significance: A glucose-transforming pathway in TGFb-driven equivalent level of EMT suppression was measured by targeting epithelial-to-mesenchymal transition provides novel mecha- the downstream enzyme sorbitol-dehydrogenase (SORD), fur- nistic insights into the metabolic control of cancer differenti- ther pointing at the involvement of the PP.
    [Show full text]
  • The Spectrum of Pyruvate Dehydrogenase Complex Deficiency
    Molecular Genetics and Metabolism 105 (2012) 34–43 Contents lists available at SciVerse ScienceDirect Molecular Genetics and Metabolism journal homepage: www.elsevier.com/locate/ymgme Minireview The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients Kavi P. Patel a, Thomas W. O'Brien b, Sankarasubramon H. Subramony c, Jonathan Shuster d, Peter W. Stacpoole a,b,⁎ a Departments of Medicine (Division of Endocrinology and Metabolism), College of Medicine, University of Florida, Gainesville, FL 32611, USA b Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA c Neurology, College of Medicine, University of Florida, Gainesville, FL 32611, USA d Epidemiology and Health Policy Research, College of Medicine, University of Florida, Gainesville, FL 32611, USA article info abstract Article history: Context: Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly Received 2 September 2011 associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, Received in revised form 27 September 2011 death during childhood. There has been no recent comprehensive analysis of the natural history and clinical Accepted 27 September 2011 course of this disease. Available online 7 October 2011 Objective: We reviewed 371 cases of PDC deficiency, published between 1970 and 2010, that involved defects in subunits E1α and E1β and components E1, E2, E3 and the E3 binding protein of the complex. Keywords: Data sources and extraction: English language peer-reviewed publications were identified, primarily by using Congenital lactic acidosis Dichloroacetate PubMed and Google Scholar search engines. Neuroimaging Results: Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency.
    [Show full text]