March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Repression of GAPDH-Mediated Telomere Protection in Müller Cells by Hyperglycemia
Author Affiliations & Notes
  • Prathiba Jayaguru
    Physiology, Michigan State University, East Lansing, Michigan
  • Sirisha Durga Yellayi
    Physiology, Michigan State University, East Lansing, Michigan
  • Ashwath Jayagopal
    Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee
  • Susanne Mohr
    Physiology, Michigan State University, East Lansing, Michigan
  • Footnotes
    Commercial Relationships  Prathiba Jayaguru, None; Sirisha Durga Yellayi, None; Ashwath Jayagopal, None; Susanne Mohr, None
  • Footnotes
    Support  NIH R01 EY-017206
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5431. doi:
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      Prathiba Jayaguru, Sirisha Durga Yellayi, Ashwath Jayagopal, Susanne Mohr; Repression of GAPDH-Mediated Telomere Protection in Müller Cells by Hyperglycemia. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5431.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important physiological role in telomere protection via direct binding to the telomere. Previously, we have shown that in high glucose conditions GAPDH accumulates in the nucleus of Müller cells in vitro and in vivo. It has been suggested that GAPDH accumulating in the nucleus under hyperglycemic conditions is post-translationally modified. How these increased levels of nuclear GAPDH affect maintenance of telomere stability in Müller cells is unknown. Therefore, the aim of the study was to investigate whether hyperglycemia alters the ability of GAPDH to protect telomere stability in these cells.

Methods: : Human (hMC) and rat (rMC-1) Müller cells were treated with normal glucose (7.8mM) or high glucose (25mM) in the presence or absence of R-(-)-Deprenyl (1nM) for 96 hours. R-(-)-Deprenyl, a monoaminooxidase inhibitor, prevents hyperglycemia-induced GAPDH nuclear accumulation. Localization of GAPDH and telomeres were determined using fluorescence in-situ hybridization and immunofluorescence staining of metaphase chromosome spreads. Telomerase activity was measured using quantitative telomerase detection kit.

Results: : Under normal conditions, there is a clear colocalization of GAPDH with the telomeres on the metaphase chromosome spreads of Müller cells. In high glucose treated cells colocalization was less prevalent, indicating the GAPDH-telomere binding is compromised. Telomerase activity was significantly decreased in high glucose treated cells (216806.3±11937.3 amoles/reaction) compared to normal glucose treated cells (354998.3±43124.1 amoles/reaction). R-(-)-Deprenyl treatment restored telomerase activity (233340.9±4480.3 amoles/reaction) and binding of GAPDH to the telomere.

Conclusions: : Although high glucose induces nuclear accumulation of GAPDH, the accumulated GAPDH failed to protect the telomeres as observed under normal conditions. This, in combination with decreased telomerase activity, potentially triggers accelerated cellular aging.

Keywords: Muller cells • aging • diabetes 

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