Nuclear GAPDH: Changing the Fate of Müller Cells in Diabetes

Overview

Journal J Ocul Biol Dis Infor

Publisher Springer

Specialty Ophthalmology

Date 2013 Mar 30

PMID 23538321

Citations 7

Authors

Prathiba Jayaguru

Susanne Mohr

Affiliations

Soon will be listed here.

Abstract

Müller cells, the primary glial cells are a crucial component of the retinal tissue performing a wide range of functions including maintaining the blood-retinal barrier. Several studies suggest that diabetes leads to Müller cell dysfunction and loss. The pathophysiology of hyperglycemia-induced cellular injury of Müller cells remains only poorly understood. Recently, the concept that translocation of the predominantly cytosolic glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to the nucleus and its accumulation in this cellular compartment alters transcriptional events associated with cell death induction has gained major interest. High glucose conditions induce nuclear translocation and accumulation of GAPDH in the nucleus of Müller cells in vivo and in vitro. With regards to Müller cell dysfunction, the effects of nuclear accumulation of GAPDH are multifaceted. Considering the functional versatility of GAPDH including gene regulation, DNA repair, telomere protection, etc., it is of immense importance to explore possible GAPDH actions to unravel the mysteries around the role of GAPDH in hyperglycemia-induced cellular changes in order to develop novel therapeutic strategies. Therefore, this review focuses on the molecular events associated with the nuclear translocation of GAPDH and how it affects the fate of Müller cells in diabetes.

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References

Fiucci G, Beaucourt S, Duflaut D, Lespagnol A, Stumptner-Cuvelette P, Geant A . Siah-1b is a direct transcriptional target of p53: identification of the functional p53 responsive element in the siah-1b promoter. Proc Natl Acad Sci U S A. 2004; 101(10):3510-5. PMC: 373493. DOI: 10.1073/pnas.0400177101. View

Mohr S, Xi X, Tang J, Kern T . Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients. Diabetes. 2002; 51(4):1172-9. DOI: 10.2337/diabetes.51.4.1172. View

Hara M, Agrawal N, Kim S, Cascio M, Fujimuro M, Ozeki Y . S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005; 7(7):665-74. DOI: 10.1038/ncb1268. View

Creagh E, Conroy H, Martin S . Caspase-activation pathways in apoptosis and immunity. Immunol Rev. 2003; 193:10-21. DOI: 10.1034/j.1600-065x.2003.00048.x. View

Demarse N, Ponnusamy S, Spicer E, Apohan E, Baatz J, Ogretmen B . Direct binding of glyceraldehyde 3-phosphate dehydrogenase to telomeric DNA protects telomeres against chemotherapy-induced rapid degradation. J Mol Biol. 2009; 394(4):789-803. PMC: 2789664. DOI: 10.1016/j.jmb.2009.09.062. View

Ronai Z . Glycolytic enzymes as DNA binding proteins. Int J Biochem. 1993; 25(7):1073-6. DOI: 10.1016/0020-711x(93)90123-v. View

House C, Hancock N, Moller A, Cromer B, Fedorov V, Bowtell D . Elucidation of the substrate binding site of Siah ubiquitin ligase. Structure. 2006; 14(4):695-701. DOI: 10.1016/j.str.2005.12.013. View

Reichenbach A, Stolzenburg J, Eberhardt W, Chao T, Dettmer D, Hertz L . What do retinal müller (glial) cells do for their neuronal 'small siblings'?. J Chem Neuroanat. 1993; 6(4):201-13. DOI: 10.1016/0891-0618(93)90042-3. View

Kannan R, Bao Y, Wang Y, Sarthy V, Kaplowitz N . Protection from oxidant injury by sodium-dependent GSH uptake in retinal Müller cells. Exp Eye Res. 1999; 68(5):609-16. DOI: 10.1006/exer.1998.0639. View

10.

Kragten E, Lalande I, Zimmermann K, Roggo S, Schindler P, Muller D . Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(-)-deprenyl. J Biol Chem. 1998; 273(10):5821-8. DOI: 10.1074/jbc.273.10.5821. View

11.

Krady J, Basu A, Allen C, Xu Y, LaNoue K, Gardner T . Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes. 2005; 54(5):1559-65. DOI: 10.2337/diabetes.54.5.1559. View

12.

Ishitani R, Tanaka M, Sunaga K, Katsube N, Chuang D . Nuclear localization of overexpressed glyceraldehyde-3-phosphate dehydrogenase in cultured cerebellar neurons undergoing apoptosis. Mol Pharmacol. 1998; 53(4):701-7. DOI: 10.1124/mol.53.4.701. View

13.

Tsacopoulos M, Magistretti P . Metabolic coupling between glia and neurons. J Neurosci. 1996; 16(3):877-85. PMC: 6578818. View

14.

Barber R, Harmer D, Coleman R, Clark B . GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genomics. 2005; 21(3):389-95. DOI: 10.1152/physiolgenomics.00025.2005. View

15.

Dastoor Z, Dreyer J . Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. J Cell Sci. 2001; 114(Pt 9):1643-53. DOI: 10.1242/jcs.114.9.1643. View

16.

House C, Frew I, Huang H, Wiche G, Traficante N, Nice E . A binding motif for Siah ubiquitin ligase. Proc Natl Acad Sci U S A. 2003; 100(6):3101-6. PMC: 152253. DOI: 10.1073/pnas.0534783100. View

17.

Tisdale E, Azizi F, Artalejo C . Rab2 utilizes glyceraldehyde-3-phosphate dehydrogenase and protein kinase C{iota} to associate with microtubules and to recruit dynein. J Biol Chem. 2008; 284(9):5876-84. PMC: 2645835. DOI: 10.1074/jbc.M807756200. View

18.

Gonzalez M, Sanz I, Silva V, Asenjo S, Gleisner A, Bustamante M . Differential modulation by native and glycated low density lipoproteins of peripheral blood mononuclear cells proliferation induced by phytohemagglutinin in insulin-dependent diabetes mellitus patients. Clin Chim Acta. 2000; 293(1-2):223-8. DOI: 10.1016/s0009-8981(99)00223-5. View

19.

Abu El Asrar A, Maimone D, MORSE P, Gregory S, Reder A . Cytokines in the vitreous of patients with proliferative diabetic retinopathy. Am J Ophthalmol. 1992; 114(6):731-6. DOI: 10.1016/s0002-9394(14)74052-8. View

20.

Joussen A, Poulaki V, Le M, Koizumi K, Esser C, Janicki H . A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004; 18(12):1450-2. DOI: 10.1096/fj.03-1476fje. View