Differential Regulation of High Glucose–Induced Glyceraldehyde-3-Phosphate Dehydrogenase Nuclear Accumulation in Müller Cells by IL-1β and IL-6

Yego, E. Chepchumba K.; Vincent, Jason; Sarthy, Vijay P.; Busik, Julia V.; Mohr, Susanne

doi:10.1167/iovs.08-2082

Cited by 71 publications

(69 citation statements)

References 47 publications

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“…hMC were isolated from the retinas of nondiabetic donors as previously described by us (4,16). After three passages, hMC cultures were 95% pure and were characterized as described previously (4,43).…”

Section: Methodsmentioning

confidence: 99%

“…The last 12 amino acids on the C-terminal in the substrate-binding domain are necessary for GAPDH-siah-1 interaction (13). The NLS motif is also located in the substratebinding domain.We have recently identified that elevated glucose levels act as a stimulus for GAPDH nuclear accumulation in retinal Müller (glia) cells via high glucose-induced activation of a caspase-1/ interleukin-1␤ signaling pathway (16 …”

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confidence: 99%

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confidence: 99%

“…Consequently, GAPDH nuclear accumulation has been suggested to participate in the development of various degenerative diseases including diabetic retinopathy (1,(3)(4)(5)(6)(7)(8)(9)11). Induction of GAPDH nuclear translocation and accumulation has been linked to the formation of oxidative stress and production of pro-inflammatory stimuli, such as nitric oxide and cytokines (2,(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

“…We have recently identified that elevated glucose levels act as a stimulus for GAPDH nuclear accumulation in retinal Müller (glia) cells via high glucose-induced activation of a caspase-1/ interleukin-1␤ signaling pathway (16). We have demonstrated that hyperglycemia-induced GAPDH nuclear accumulation not only occurs in retinal Müller cells in vitro but also in vivo during the development of diabetic retinopathy in rodents (4).…”

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confidence: 99%

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siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

Yego

Mohr

2010

Journal of Biological Chemistry

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The translocation and accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the nucleus has closely been associated with cell death induction. However, the mechanism of this process has not been completely understood. The E3 ubiquitin ligase siah-1 (seven in absentia homolog 1) has recently been identified as a potential shuttle protein to transport GAPDH from the cytosol to the nucleus. Previously, we have demonstrated that elevated glucose levels induce GAPDH nuclear accumulation in retinal Müller cells. Therefore, this study investigated the role of siah-1 in high glucose-induced Several reports have demonstrated that the nuclear translocation and accumulation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 2 play important roles in early events leading to cell death initiation and execution (1, 2). Consequently, GAPDH nuclear accumulation has been suggested to participate in the development of various degenerative diseases including diabetic retinopathy (1, 3-9, 11). Induction of GAPDH nuclear translocation and accumulation has been linked to the formation of oxidative stress and production of pro-inflammatory stimuli, such as nitric oxide and cytokines (2,(11)(12)(13)(14)(15)(16).Although some events and stimuli leading to GAPDH nuclear accumulation have been identified, the mechanism of movement of GAPDH from the cytosol to the nucleus is unclear. GAPDH lacks a common nuclear localization signal (NLS) and therefore cannot enter the nucleus by itself because of its size. A recent study has identified the E3 ubiquitin ligase siah-1 (seven in absentia homolog 1) as a potential carrier/shuttle protein (13). According to this study, GAPDH binds the NLS-bearing siah-1, forming a complex subsequently promoting translocation of GAPDH from the cytosol to the nucleus. It is postulated that the NLS on siah-1 facilitates the nuclear movement of the complex.siah-1 proteins are human homologs of the evolutionarily conserved Drosophila, E3 ubiquitin ligase sina (seven in absentia) protein (17). sina was first identified as a key protein during R7 photoreceptor development in the Drosophila fruit fly whereby it facilitates the degradation of the transcriptional repressor of neuronal fate tramtrack (TTK88) (18 -20). Follow-up studies have identified functions for siah-1 in various cellular processes including mitosis, neuronal plasticity, development, angiogenesis, inflammation, and cell death (13, 17, 20 -29). Two siah genes, siah-1 and siah-2 are present in humans and rats, whereas mice have three siah genes: siah-1a, siah-1b, and siah-2 (17, 30, 31). siah-1a and siah-1b have 98% sequence homology. Structurally, siah-1 contains an N-terminal RING domain that facilitates the ligase function, two cysteine-rich zinc finger domains, and a substrate-binding domain, which is localized on the C-terminal of the protein (27,32,33). The last 12 amino acids on the C-terminal in the substrate-binding domain are necessary for GAPDH-siah-1 interaction (13). The NLS motif is also located in the ...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

Yego

Mohr

2010

Journal of Biological Chemistry

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Subcellular dynamics of multifunctional protein regulation: Mechanisms of GAPDH intracellular translocation

Sirover

2012

J of Cellular Biochemistry

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Multidimensional proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibit distinct activities unrelated to their originally identified functions. Apart from glycolysis, GAPDH participates in iron metabolism, membrane trafficking, histone biosynthesis, the maintenance of DNA integrity and receptor mediated cell signaling. Further, multifunctional proteins exhibit distinct changes in their subcellular localization reflecting their new activities. As such, GAPDH is not only a cytosolic protein but is localized in the membrane, the nucleus, polysomes, the ER and the Golgi. In addition, although the initial subcellular localizations of multifunctional proteins may be of significance, dynamic changes in intracellular distribution may occur as a consequence of those new activities. As such, regulatory mechanisms may exist through which cells control multifunctional protein expression as a function of their subcellular localization. The temporal sequence through which subcellular translocation and the acquisition of new GAPDH functions is considered as well as post-translational modification as a basis for its intracellular transport.

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Reduced gap junctional communication among astrocytes in experimental diabetes: Contributions of altered connexin protein levels and oxidative–nitrosative modifications

Ball

Harik

Gandhi

et al. 2011

J of Neuroscience Research

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Experimental diabetes increases production of reactive oxygen-nitrogen species and inhibits astrocytic gap junctional communication in tissue culture and brain slices from streptozotocin (STZ)-diabetic rats by unidentified mechanisms. Relative connexin (Cx) protein levels were assessed by Western blotting using extracts from cultured astrocytes grown in high (25 mmol/L) or low (5.5 mmol/L) glucose for 2–3 weeks and STZ-diabetic rat brain. Chemiluminescent signals for diabetic samples were normalized to those of controls on the same blot and same protein load. Growth in high glucose did not alter relative Cx26 level, whereas Cx30 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were reduced by ~30% and Cx43 increased ~1.9-fold. In the inferior colliculus of STZ-diabetic rats, Cx30 and Cx43 levels in three of four rats were half those of controls, whereas GAPDH and actin were unaffected. Diabetes did not affect levels of Cx30, Cx43, and GAPDH in cerebral cortex, but actin level rose 24%. Cx43 was predominantly phosphorylated in control and diabetic samples, so reduced dye transfer is not due to overall dephosphorylation of Cx43. Astrocytic growth in high glucose reduced dye-labeled area by 75%, but 10 min treatment with dithiothreitol restored normal dye transfer. In contrast, nitric oxide donors inhibited dye transfer among astrocytes grown in low glucose by 50–65% within 1h. Thus, modifications arising from oxidative-nitrosative stress, not altered connexin levels, may underlie reduced dye transfer among severely-hyperglycemic cultured astrocytes, whereas both oxidative-nitrosative stress and regionally-selective down-regulation of connexin protein content may affect gap junctional communication in brain of STZ-diabetic rats.

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Differential Regulation of High Glucose–Induced Glyceraldehyde-3-Phosphate Dehydrogenase Nuclear Accumulation in Müller Cells by IL-1β and IL-6

Cited by 71 publications

References 47 publications

siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

siah-1 Protein Is Necessary for High Glucose-induced Glyceraldehyde-3-phosphate Dehydrogenase Nuclear Accumulation and Cell Death in Müller Cells

Subcellular dynamics of multifunctional protein regulation: Mechanisms of GAPDH intracellular translocation

Reduced gap junctional communication among astrocytes in experimental diabetes: Contributions of altered connexin protein levels and oxidative–nitrosative modifications

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