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[{"key": "dc.contributor.advisor", "value": "Lehti, Maarit", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Lehtola, Anette", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2015-09-15T17:20:05Z", "language": "", "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2015-09-15T17:20:05Z", "language": "", "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2015", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1495654", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/46824", "language": "", "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "HDL:n (high density lipoprotein) p\u00e4\u00e4proteiinikomponentin, apolipoproteiini A1:n (ApoA1), on todettu\r\nlis\u00e4\u00e4v\u00e4n glykolyysia ja oksidatiivista fosforylaatiota hiiren luurankolihassoluissa. ApoA1:ll\u00e4 oletetaan my\u00f6s\r\nolevan merkitt\u00e4v\u00e4 rooli lihaksen normaalissa aineenvaihdunnassa ja siihen liittyviss\u00e4 sairauksissa. ApoA1\r\nvaikuttaa leukosyyttien aktivaatioon ja jakautumiseen s\u00e4\u00e4telem\u00e4ll\u00e4 solun sis\u00e4ist\u00e4 kolesterolitasoa. N\u00e4m\u00e4\r\nmuutokset vaikuttavat my\u00f6s solun aineenvaihduntaan. ApoA1:n suoranaista vaikutusta leukosyyttien\r\nsoluhengitykseen ei kuitenkaan ole aiemmin tutkittu. Aiemmin on esitetty, ett\u00e4 leukosyyttej\u00e4 voitaisiin\r\nk\u00e4ytt\u00e4\u00e4 biomarkkerina kuvaamaan muutoksia mitokondrioiden toiminnassa aineenvaihduntaan liittyv\u00e4n\r\nstressin aikana. Er\u00e4\u00e4ss\u00e4 tutkimuksessa leukosyyttien mitokondrioita k\u00e4ytettiin onnistuneesti kuvaamaan\r\nfysiologisia muutoksia syd\u00e4nlihassoluissa. T\u00e4m\u00e4n pro gradu -tutkimuksen taustalla on tulevaisuuden\r\np\u00e4\u00e4m\u00e4\u00e4r\u00e4 siit\u00e4, ett\u00e4 leukosyyttien mitokondrioiden avulla voitaisiin kuvata lihassoluissa tapahtuvia ApoA1\r\nv\u00e4litteisi\u00e4 aineenvaihdunnan muutoksia. T\u00e4ss\u00e4 tutkimuksessa tavoitteena on selvitt\u00e4\u00e4 vaikuttaako ApoA1\r\nsamoin leukosyyttien soluhengitykseen, kuin sen on aiemmin esitetty vaikuttavan lihassolujen\r\nsoluhengitykseen. Tutkimuksella on kaksi hypoteesia: 1) ApoA1 lis\u00e4\u00e4 soluhengityst\u00e4 ja 2) ApoA1 vaikuttaa\r\nsoluhengityskompleksiproteiinien m\u00e4\u00e4r\u00e4\u00e4n leukosyyteiss\u00e4. Soluviljelyolosuhteissa kasvavat ihmisen T\r\nlymfosyytit altistettiin ApoA1:lle 50 \u00b5g/ml konsentraatiossa 4, 12 tai 24 tunnin ajan. Muutoksia\r\nsoluhengityksess\u00e4 monitoroitiin korkean resoluution respirometrill\u00e4 kokonaisissa (4, 12, 24h) ja l\u00e4p\u00e4istyiss\u00e4\r\n(12h) soluissa. L\u00e4p\u00e4istyjen solujen avulla pystyttiin tutkimaan kullekkin hengityskompleksille ominaista\r\nsoluhengityst\u00e4. ApoA1:n vaikutusta hengityskompleksiproteiinien m\u00e4\u00e4r\u00e4\u00e4n tutkittiin western blot \u2013\r\nmenetelm\u00e4ll\u00e4 k\u00e4ytt\u00e4en viiden vasta-aineen sekoitusta. Soluhengitys oli tilastollisesti merkitt\u00e4v\u00e4sti lis\u00e4\u00e4ntynyt\r\nROUTINE (p= 0.040) ja ETS (p= 0.011) hengitystiloissa kokonaisissa soluissa, joita oli altistettu ApoA1:lle\r\n4 tunnin ajan. ROUTINE hengitystila kuvaa kokonaisten solujen soluhengityst\u00e4 kasvatusmediumin\r\nsubstraateilla. ETS hengitystila kuvaa oksidatiiviseen fosforylaatioon liittyv\u00e4n elektroninsiirron\r\nmaksimaalista kapasiteettia. ApoA1:lle 4 tunnin ajan altistetuissa soluissa ROUTINE hengitystila oli\r\nkauempana ETS hengitystilasta (p= 0.035), kuin kontrolli soluissa. Hengityskompleksi IV:n proteiinim\u00e4\u00e4r\u00e4\r\noli alentunut (p= 0.018) ApoA1:lle altistetuissa soluissa. Hengityskompleksikohtainen hengitys ei tuottanut\r\ntilastollisesti merkitt\u00e4vi\u00e4 tuloksia. Kokonaisilla soluilla saadut tulokset vahvistivat ensimm\u00e4isen hypoteesin.\r\nN\u00e4m\u00e4 tulokset osoittavat ett\u00e4 ApoA1 lis\u00e4\u00e4 ETS kapasiteettia leukosyyteiss\u00e4. Lis\u00e4\u00e4ntynyt ETS kapasiteetti\r\nnostaa my\u00f6s ROUTINE \u2013tilan hengityst\u00e4 ja ylij\u00e4\u00e4m\u00e4 hengitystasoa. Toinen hypoteesi vahvistettiin my\u00f6s,\r\nsill\u00e4 hengityskompleksi CIV:n proteiinim\u00e4\u00e4r\u00e4 oli merkitt\u00e4v\u00e4sti alentunut. T\u00e4m\u00e4n tutkimuksen perusteella\r\nvoidaan todeta ett\u00e4 ApoA1 lis\u00e4\u00e4 soluhengityst\u00e4 kokonaisissa leukosyyteiss\u00e4 ja muokkaa\r\nsoluhengityskompleksien proteiineja. On kuitenkin otettava huomioon, ett\u00e4 t\u00e4m\u00e4 tutkimus on alustava ja\r\ntoteutettu pienell\u00e4 n\u00e4ytem\u00e4\u00e4r\u00e4ll\u00e4. Tulosten varmistamiseksi on suotavaa tehd\u00e4 viel\u00e4 lis\u00e4tutkimuksia\r\nsuuremmalla n\u00e4ytem\u00e4\u00e4r\u00e4ll\u00e4. L\u00e4p\u00e4istyist\u00e4 soluista ei onnistuttu saamaan merkitsevi\u00e4 tuloksia, sill\u00e4 metodissa\r\nhavaittiin useita artifaktoja. Hengityskompleksikohtaista hengityst\u00e4 olisi syyt\u00e4 tutkia tulevaisuudessa, ett\u00e4\r\nsaataisiin tarkempaa tietoa ApoA1:n vaikutuksesta soluhengitysketjun eri osiin.. T\u00e4ss\u00e4 havaitut tulokset ovat\r\nkaikesta huolimatta lupaavia leukosyyttien biomarkkerina k\u00e4yt\u00f6n tulevaisuuden kannalta.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "The main protein component of high density lipoprotein (HDL), apolipoprotein A1 (ApoA1), has previously\r\nbeen shown to stimulate glycolysis and mitochondrial oxidative phosphorylation in mouse muscle cells.\r\nApoA1 is also suggested to have a role in normal metabolism and metabolic diseases in skeletal muscle. In\r\nleukocytes, by regulating cellular cholesterol, ApoA1 is able to affect leukocyte cell activation and\r\nproliferation and through these actions, cell metabolism can be changed. However, direct effects of ApoA1 to\r\nleukocyte cell respiration have not been studied. Leukocytes have been suggested to function as predictive\r\nbiomarkers of mitochondrial function under metabolic stress. Leukocyte mitochondria have previously been\r\nused to reflect physiological changes in heart muscle cells and the ultimate target is that leukocytes could be\r\nused to reflect ApoA1 related metabolic changes in muscle cells. The aim of this preliminary study was to\r\nexamine whether ApoA1 has similar effect on leukocyte cell respiration, as it does on mouse muscle\r\nmitochondria. First hypothesis is that ApoA1 increases human leukocyte cell respiration and second\r\nhypothesis is that ApoA1 affects the amount of respiration complex proteins in human leukocytes. To\r\nexamine the effect of ApoA1 to cell respiration, cultured human T lymphocytes were incubated for 4, 12 or\r\n24 hours with 50 \u00b5g/ml of ApoA1. Cell respiration was studied with high resolution respirometry in intact\r\n(4h, 12h, 24h) cells and complex specific respiration was studied with permeabilized cells (12h). Glutamate,\r\nmalate, succinate, ADP, oligomycin, CCCP, rotenone and antimycin A were used to induce different\r\nrespiration states. Effect of ApoA1 on respiration complex proteins was determined with western blot using\r\nantibody cocktail for proteins of five different respiration complexes. Increase in cell respiration was\r\nstatistically significant at ROUTINE respiration (p= 0.040) and ETS capacity (p= 0.011) in intact cells\r\ntreated with ApoA1 for 4 hours. ROUTINE respiration reflects respiration in intact cells by growth medium\r\nsubstrates. ETS capacity reflects the maximal capacity of oxidative phosphorylation related electron transfer.\r\nROUTINE control ratio was significantly decreased (p= 0.035) in 4 hours ApoA1 treated intact cells. This\r\nindicates that ROUTINE respiration is operating closer to ETS capacity in control cells than in ApoA1 cells.\r\nRespiration complex IV proteins were significantly decreased in ApoA1 treated cells (p= 0.018). Complex\r\nspecific respiration in permeabilized cells was not significantly affected by ApoA1 treatment. First\r\nhypothesis was confirmed by results obtained with intact cells. These results indicate ApoA1 increased ETS\r\ncapacity in leukocytes. Increased ETS capacity leads to increased ROUTINE respiration and residual\r\nrespiration. Second hypothesis was confirmed since significant decrease in CIV protein was discovered with\r\nwestern blot. Based on this study, it can be concluded that ApoA1 increases cell respiration in intact\r\nleukocytes and affects respiration complex proteins. However, this study was limited preliminary study and\r\nfurther experiments with larger sample size are needed to confirm the obtained results. Due to several\r\nartifacts significant results were not obtained regarding complex specific respiration in permeabilized cells.\r\nRespiration in permeabilized cells should be examined in future studies to gain knowledge of more detailed\r\neffects of ApoA1 to cell respiration. Nonetheless the results obtained here are promising for the future use of\r\nleukocytes to reflect metabolism in muscle cells.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Anette Lehtola (anmikrle) on 2015-09-15 17:20:05.116180. Form: Pro gradu -lomake (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake). JyX data: [jyx_publishing-allowed (fi) =True]", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by jyx lomake-julkaisija (jyx-julkaisija.group@korppi.jyu.fi) on 2015-09-15T17:20:05Z\r\nNo. of bitstreams: 2\r\nURN:NBN:fi:jyu-201509152880.pdf: 968321 bytes, checksum: 82ab8424e1167eae0ccb2d42d427215d (MD5)\r\nlicense.html: 4865 bytes, checksum: 577beb42fd683e1d8d2d7df72f503665 (MD5)", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2015-09-15T17:20:05Z (GMT). No. of bitstreams: 2\r\nURN:NBN:fi:jyu-201509152880.pdf: 968321 bytes, checksum: 82ab8424e1167eae0ccb2d42d427215d (MD5)\r\nlicense.html: 4865 bytes, checksum: 577beb42fd683e1d8d2d7df72f503665 (MD5)\r\n Previous issue date: 2015", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (44 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.title", "value": "Main protein component of high density lipoprotein, apolipoprotein A1, modulates leukocyte cell respiration", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201509152880", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.date.updated", 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