Role of X-box Binding Protein 1 in Regulation of Retinal Müller Glia Metabolism
Başlık:
Role of X-box Binding Protein 1 in Regulation of Retinal Müller Glia Metabolism
Yazar:
Kelly, Kristen, author.
ISBN:
9780438050747
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (52 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Sarah X. Zhang Committee members: Malcolm Slaughter; Joshua J. Wang.
Özet:
Muller glia play a critical role in maintaining retinal homeostasis through shuttling metabolic substrates to and from retinal neurons, releasing trophic factors, regulating neurotransmission, providing structural support, and regulating the extracellular environment. Thus, studying the regulation of Muller glia metabolism could provide helpful insights for understanding retinal dysfunction and degeneration. In this study, we investigate the role of X-box binding protein 1 (XBP1), a stress-inducible transcription factor, in regulation of retinal Muller glial metabolism. We hypothesize that deletion of XBP1 in Muller glia leads to increases in glycolytic capacity, which could in turn alter retinal metabolism. To test this hypothesis, we generated XBP1 conditional knockout (cKO) mice that lack XBP1 specifically in Muller glia using the Cre/LoxP system. Using a Seahorse extracellular flux metabolic analyzer, we measured mitochondrial respiration and glycolysis in the retina and in isolated Muller cells from XBP1 cKO mice. Our results demonstrate an increased rate of glycolysis in XBP1 cKO retinas and in XBP1-deficient Muller cells. These changes are associated with elevated glucose uptake and upregulation of glucose transporters GLUT1 and GLUT2. Additionally, two regulatory enzymes involved in glycolysis, pyruvate kinase and Hexokinase 1, are also upregulated in XBP1 cKO Muller cells. Taken together, our data suggest that XBP1 plays an important role in regulation of glucose metabolism in retinal Muller glia, which, although consisting of a relatively small population of retinal cells, could consequently influence retinal metabolic profile and function.
Notlar:
School code: 0656
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(694357.1) | 694357-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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