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[{"key": "dc.contributor.advisor", "value": "Hulmi, Juha", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Kolari, Kalle", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2023-08-15T05:01:44Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2023-08-15T05:01:44Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2023", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/88521", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Pro-gradu tutkimuksen tarkoituksena on tuoda lis\u00e4tietoa glykolyysin rinnakkaisen aineenvaihduntareitin, seriinisynteesin, roolista C2C12 lihassolujen jakaantumis- hypertrofia potentiaaliin. Potentiaalin muutoksia tarkastellaan est\u00e4m\u00e4ll\u00e4 kemiallisesti seriinisynteesin toimintaa. Samalla seurataan 14C isotoopin kulkeutumista seriinisynteesireitiss\u00e4 muodostuneisiin biomolekyyleihin. Lis\u00e4ksi tutkitaan, aiheuttaako kemialliset inhibiittorit NCT- 503 ja CBR-5884 samankaltaisia vaikutuksia. Lopuksi tarkastellaan, muuttuuko glukoosin k\u00e4ytt\u00f6 biomolekyylien valmistamisessa. Seriini synteesi aineenvaihduntareitin on havaittu olevan merkitt\u00e4v\u00e4 solun kasvun ja jakautumisen kannalta. Sen on havaittu olevan merkitt\u00e4v\u00e4 l\u00e4ht\u00f6aine muiden biomolekyylien esiasteiden valmistamisessa. Kirjallisuutta aineenvaihduntareitin roolista lihassolun jakautumisen ja koon kasvun n\u00e4k\u00f6kulmasta on v\u00e4h\u00e4isesti. T\u00e4ten seriini synteesi aineenvaihduntareitin tutkiminen lihassoluissa tuottaa mahdollisesti lis\u00e4tietoa seriinisynteesin roolista lihassolun jakautumisen ja hypertrofia potentiaalin n\u00e4k\u00f6kulmasta.\nIhmiskehossa on keskim\u00e4\u00e4rin 40 % lihaskudosta. Lihaskudoksella on t\u00e4rke\u00e4 rooli aineenvaihdunnallisessa terveydess\u00e4. Lihasmassa toimii niin aminohappo- kuin glykogeeni varastona. Lis\u00e4ksi lihaskudos on yksi t\u00e4rkeimmist\u00e4 glukoositasapainon s\u00e4\u00e4telij\u00f6ist\u00e4. 1900- luvun alussa Warburg havaitsi, ett\u00e4 jakaantuvat solut lis\u00e4\u00e4v\u00e4t glukoosin kulutusta my\u00f6s aerobisissa olosuhteissa. Ilmi\u00f6 nimettiin Warburgin efektiksi. On ehdotettu, ett\u00e4 lis\u00e4\u00e4ntynyt glukoosin k\u00e4ytt\u00f6 soluissa edist\u00e4isi solun jakautumista sek\u00e4 kasvua tuottamalla aineenvaihduntatuotteita. Yksi merkitt\u00e4vimmist\u00e4 aineenvaihduntareiteist\u00e4 on seriinisynteesi, joka tuottaa aminohappo seriini\u00e4. Seriini\u00e4 voidaan k\u00e4ytt\u00e4\u00e4 proteiinien, RNA:n sek\u00e4 lipidien valmistamisen esiasteena. Seriinisynteesireitin entsyymi fosfoglyseraatti dehydrogenaasi, PHGDH, muuttaa glykolyysin v\u00e4lituotteen 3-fosfoglyseraatin 3-fosfohydroksipyruvaatiksi, josta se edelleen muokataan seriiniksi. PHGDH entsyymin manipulaatio voidaan suorittaa entsyymin toimintaa heikent\u00e4vill\u00e4 yhdisteill\u00e4 kuten NCT-503:lla sek\u00e4 CBR-5884:lla. Muutoksia lihassolun jakautumisen ja hypertrofian potentiaalissa PHGDHn manipulaation seurauksena tutkitaan 14C isotooppileimauskokeilla. 14C ker\u00e4\u00e4ntymist\u00e4 makromolekyyleihin seurataan. Solukokeissa soluille annetaan leimattua glukoosia tai valiinia ja osalle soluista lis\u00e4t\u00e4\u00e4n kemiallinen k\u00e4sittely heikent\u00e4en PHGDH:n toimintaa. Tuloksia verrataan erist\u00e4m\u00e4ll\u00e4 ei-k\u00e4sitellyist\u00e4 ja k\u00e4sitellyist\u00e4 soluista biomolekyylit ja mitataan kokonaisradioaktiivisuus jokaisessa makromolekyyli n\u00e4ytteess\u00e4. Mit\u00e4 v\u00e4hemm\u00e4n on kokonaisradioaktiivisuutta, sit\u00e4 v\u00e4hemm\u00e4n leimattua glukoosia on k\u00e4ytetty makromolekyylien valmistamisessa.\nSeriini synteesi aineenvaihdunta reitin kemiallinen heikennys NCT-503 sek\u00e4 CBR-5884 yhdisteell\u00e4 heikensi selke\u00e4sti lihassoli jakautumis- ja hypertrofiapotentiaalia. Kemiallinen k\u00e4sittely v\u00e4hensi 14C hiilien kertymisen leimatusta glukoosista proteiineihin, RNA:han sek\u00e4 lipideihin verrattuna ei-k\u00e4sitellyist\u00e4 soluista eristettyihin makromolekyyleihin. T\u00e4ll\u00f6in lihassolu ei voi tehokkaasti valmistaa solun jakautumiseen vaadittavia makromolekyylej\u00e4. Valtaosa leimatusta hiilest\u00e4 glukoosista p\u00e4\u00e4tyi proteiineihin, jolloin glukoosin rooli tulosten perusteella voi olla suuri aminohappojen valmistamisessa vahvistaen aminohappojen roolia lihassolujen jakautumisessa sek\u00e4 kasvussa. Glukoosin osuus makromolekyylien valmistamisessa havaittiin vaihtelevan. T\u00e4m\u00e4 voidaan havaita siin\u00e4, kuinka voimakas 14C kokonaisradioaktiivisuus v\u00e4henee makromolekyyleiss\u00e4 kemiallisen k\u00e4sittelyn seurauksena. Suurempi v\u00e4heneminen on mahdollisesti yhteydess\u00e4 suurempaan glukoosin rooliin. Lis\u00e4ksi inhibiittoreilla esiintyy potentiaalisesti vaikutuseroja.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "The purpose of the thesis is to elaborate the role of serine synthesis pathway, a metabolic pathway parallel to glycolysis, in the potential of C2C12 muscle cells to proliferate and grow. Changes in potential are examined by chemically inhibiting the activity of serine synthesis pathway. At the same time, the net incorporation of the 14C isotope to the biomolecules formed in the serine synthesis pathway is examined. In addition, it is investigated whether the chemical inhibitors NCT-503 and CBR-5884 have similar inhibition effects to biomolecule synthesis. Finally, the changes in utilization of glucose in the synthesis of biomolecules are examined. The serine synthesis pathway has been found to be important for cell growth and division. Serine synthesis pathway has been found to be a significant contributor in formation of precursor molecules for synthesis of other biomolecules. The literature on the role of the pathway in muscle cell division and growth is sparce. Thus, examining aforementioned pathway in muscle cells potentially yields valuable information about its role in muscle cell division and hypertrophy potential.\nThe human body has an average of 40% muscle tissue. Muscle tissue plays an important role in metabolic health. Muscle mass acts as both amino acid and glycogen storage. In addition, muscle tissue is one of the most important regulators of glucose balance. At the beginning of the 20th century, Warburg discovered that dividing cells increase glucose consumption even under aerobic conditions. The phenomenon was named as the Warburg effect. It has been suggested that the increased use of glucose in cells would promote cell division and growth by producing metabolic byproducts. One of the most significant metabolic pathways is serine synthesis, which produces the amino acid serine. Serine can be used as a precursor for the production of proteins, RNA and lipids. The serine synthesis pathway enzyme phosphoglycerate dehydrogenase, PHGDH, converts the glycolysis intermediate 3- phosphoglycerate into 3-phosphohydroxypyruvate, from which it is further modified into serine. Manipulation of the PHGDH enzyme can be performed with compounds that weaken the activity of the enzyme, such as NCT-503 and CBR-5884. Changes in muscle cell division and hypertrophy potential as a result of PHGDH manipulation are investigated with 14C isotope labeling experiments. 14C accumulation in macromolecules is monitored. In cell experiments, the cells are given labeled glucose or valine and chemical treatment is added to some of the cells, weakening the function of PHGDH. The results are compared by isolating biomolecules from untreated and treated cells and measuring the total radioactivity in each macromolecule sample. The less total radioactivity there is, the less labeled glucose has been used to make the macromolecules.\nThe chemical weakening of the serine synthesis pathway with the compound NCT-503 and CBR-5884 clearly weakened the muscle cell division and hypertrophy potential. Chemical treatment reduced the accumulation of 14C carbons from labeled glucose to proteins, RNA and lipids compared to macromolecules isolated from untreated cells. In this case, the muscle cell cannot efficiently produce the macromolecules required for cell division. Most of the labeled carbon glucose ended up in proteins, so based on the results, the role of glucose may be considered significant in the production of amino acids, highlighting the role of amino acids in the division and growth of muscle cells. The utilization of glucose in the production of macromolecules was found to vary. This can be observed in how noticeable the total 14C radioactivity decreases in macromolecules as a result of chemical treatment. The greater reduction may be associated to a greater role of glucose in biomolecule synthesis. In addition, there are potentially differences in effects with inhibitors.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2023-08-15T05:01:44Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2023-08-15T05:01:44Z (GMT). No. of bitstreams: 0\n Previous issue date: 2023", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "63", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": null, "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.title", "value": "Role of serine synthesis pathway parallel to glycolysis in C2C12 muscle cell proliferation and myotube hypertrophy potential : effect of phosphoglycerate dehydrogenase inhibition", "language": "", "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-202308154632", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Liikuntatieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sport and Health Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Liikunta- ja terveystieteet", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Sport and Health Sciences", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Liikuntafysiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Exercise Physiology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.copyright", "value": "\u00a9 The Author(s)", "language": null, "element": "rights", "qualifier": "copyright", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "5011", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "RNA", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "lihassolut", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "aminohapot", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "entsyymit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "isotoopit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteiinit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "biomolekyylit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "RNA", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "muscle cells", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "amino acids", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "enzymes", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "isotopes", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteins", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "biomolecules", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/collections/archival-workstation).", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/kokoelmat/arkistotyoasema..", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}]
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