May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
High Glucose-Induced Complex Formation of Glyceraldehyde-3-Phosphate Dehydrogenase With Seven in Absentia Homolog-1 Protein: A Possible Mechanism for Apoptosis Induction in Retinal Müller Cells
Author Affiliations & Notes
  • E. K. Yego
    Case Western Reserve University, Cleveland, Ohio
    Physiology and Biophysics,
  • S. Mohr
    Case Western Reserve University, Cleveland, Ohio
    Physiology and Biophysics, Medicine, and Ophthalmology,
  • Footnotes
    Commercial Relationships E.K. Yego, None; S. Mohr, None.
  • Footnotes
    Support NIH Training Grant 2T32EY07157-06 (EY) and NIH Grant EY014380(SM)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1359. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      E. K. Yego, S. Mohr; High Glucose-Induced Complex Formation of Glyceraldehyde-3-Phosphate Dehydrogenase With Seven in Absentia Homolog-1 Protein: A Possible Mechanism for Apoptosis Induction in Retinal Müller Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1359. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: Müller cell dysfunction has been suggested to contribute to the development of diabetic retinopathy. Previously, we have demonstrated that high glucose induces glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear accumulation in retinal Müller cells in vitro and in vivo, a process which is dependent on the activation of the caspase-1/interleukin-1ß (IL-1ß) signaling pathway subsequently leading to apoptosis of these cells. The mechanism of GAPDH translocation to and accumulation in the nucleus is unclear because GAPDH lacks a nuclear localization signal (NLS). Recent studies done in macrophages demonstrated that complex formation of GAPDH with seven in absentia homolog-1 (siah-1), which has a NLS, is necessary for GAPDH translocation to the nucleus. Therefore, this study was focused on identifying (1) whether high glucose leads to siah-1 up-regulation and (2) whether GAPDH forms a complex with siah-1.

Methods:: Transformed rat retinal Müller (rMC-1) cells were incubated with normal (5mM) glucose medium or high (25mM) glucose medium for up to 96 hours. Following high glucose incubation cytosolic siah-1 amounts were determined by Western Blot analysis. To examine GAPDH/siah-1 complex formation, co-immunoprecipitation experiments were performed.

Results:: High glucose induced a two-fold increase in siah-1 protein levels starting at 5 hours of high glucose treatment. Elevated siah-1 protein levels were sustained under hyperglycemic conditions for up to 96 hours. Further, GAPDH/siah-1complex formation was detected at 12 hours of high glucose treatment. This interaction was inhibited by a caspase-1 inhibitor (YVAD-fmk).

Conclusions:: High glucose-induced siah-1 up-regulation and subsequent complex formation with GAPDH presents a possible mechanism by which GAPDH translocates from the cytosol into the nucleus to induce apoptosis. Inhibition of caspase-1 prevented GADPH/siah-1 complex formation indicating that a caspase-1/IL-1ß signaling driven mechanism contributes to this process subsequently leading to Müller cell dysfunction and the development of diabetic retinopathy.

Keywords: diabetic retinopathy • Muller cells • apoptosis/cell death 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×