GAPDH in Anesthesia

Seidler, Norbert W.

doi:10.1007/978-94-007-4716-6_9

Cited by 6 publications

(7 citation statements)

References 91 publications

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“…This study extends our previous suggestion that GAPDH plays a role in anesthesia [30]. Our current data suggests that GAPDH may be organizing the structure of the membrane (Figure 3) through its interaction with the phospholipids.…”

Section: Discussionsupporting

confidence: 91%

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABA_A Receptor Trafficking

Montalbano

Theisen

Fibuch

et al. 2012

ISRN Anesthesiology

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GABA A receptor activity is directly modulated by glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a protein with many nonglycolytic moonlighting functions. In addition to playing a role in the phosphorylation of the receptor, GAPDH may also participate in proper receptor trafficking to the plasma membrane. We previously showed that volatile anesthetics affect GAPDH structure and function that may contribute to the manner by which GAPDH modulates the GABA A receptor. In the current study, GAPDH interacted with engineered phospholipid-containing vesicles, preferring association with phosphatidylserine over phosphatidylcholine. Phosphatidyl-serine is known to participate in membrane trafficking of transport proteins and to play a role in GABA A receptor stability and function. We observed that GAPDH promoted the self-association and fusion of phosphatidylserine-rich vesicles as well as decreased membrane fluidity. Isoflurane enhanced each of these GAPDH-mediated events. Isoflurane also increased the binding of GAPDH to the cytoplasmic loop of the GABA A receptor. These observations are consistent with the working model of isoflurane playing a role in the trafficking of membrane proteins. This study is the first to implicate GAPDH and isoflurane in the regulation of GABA A receptor localization, providing insight into the mechanism of action of anesthesia.

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Section: Discussionsupporting

confidence: 91%

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABA_A Receptor Trafficking

Montalbano

Theisen

Fibuch

et al. 2012

ISRN Anesthesiology

Self Cite

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“…Due to these properties, OxyR is considered the H 2 O 2 sensor in bacteria (reviewed by Marinho et al, 2014 ). GAPDH can be reversible inhibited by H 2 O 2 at more moderate rates (500 M −1 s −1 ) ( Little and O’Brien, 1969 ; Winterbourn and Hampton, 2008 ; Peralta et al, 2015 ), still more reactive than free Cys; and GAPDH is highly abundant (∼240 μM) ( Sneider, 2013 ). Furthermore, most cells contain high amounts of GSH that can also outcompete for H 2 O 2 ( Winterbourne and Hampton, 2008 ).…”

Section: H 2 O 2 Signaling Thoumentioning

confidence: 99%

The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction

Netto

Antunes

2016

Molecules and Cells

201

115

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A challenge in the redox field is the elucidation of the molecular mechanisms, by which H2O2 mediates signal transduction in cells. This is relevant since redox pathways are disturbed in some pathologies. The transcription factor OxyR is the H2O2 sensor in bacteria, whereas Cys-based peroxidases are involved in the perception of this oxidant in eukaryotic cells. Three possible mechanisms may be involved in H2O2 signaling that are not mutually exclusive. In the simplest pathway, H2O2 signals through direct oxidation of the signaling protein, such as a phosphatase or a transcription factor. Although signaling proteins are frequently observed in the oxidized state in biological systems, in most cases their direct oxidation by H2O2 is too slow (101 M−1s−1 range) to outcompete Cys-based peroxidases and glutathione. In some particular cellular compartments (such as vicinity of NADPH oxidases), it is possible that a signaling protein faces extremely high H2O2 concentrations, making the direct oxidation feasible. Alternatively, high H2O2 levels can hyperoxidize peroxiredoxins leading to local building up of H2O2 that then could oxidize a signaling protein (floodgate hypothesis). In a second model, H2O2 oxidizes Cys-based peroxidases that then through thiol-disulfide reshuffling would transmit the oxidized equivalents to the signaling protein. The third model of signaling is centered on the reducing substrate of Cys-based peroxidases that in most cases is thioredoxin. Is this model, peroxiredoxins would signal by modulating the thioredoxin redox status. More kinetic data is required to allow the identification of the complex network of thiol switches.

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“…Histone H1 is part of the histone complex around which the DNA is tightly wrapped and which together with the DNA forms the basic unit of chromatin, the nucleosome [ 79 ]. GAPDH serves an important metabolic function in eukaryotic cells as it catalyses the breakdown of glucose during glycolysis, a process which takes place in the cytosol [ 80 ]. HSP90 is a molecular chaperone, which guides efficient protein folding of many newly synthesized proteins in the cytosol [ 81 ].…”

Section: Methodsmentioning

confidence: 99%

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5

et al. 2015

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Adult cardiac stem cells (CSCs) express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd)—a co-activator not only for serum response factor, but also for Gata4 and Tbx5—is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT), and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains). MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized. In summary: (1) GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2) Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3) Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate.

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GAPDH in Anesthesia

Cited by 6 publications

References 91 publications

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABA_A Receptor Trafficking

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABA_A Receptor Trafficking

The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5

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GAPDH in Anesthesia

Cited by 6 publications

References 91 publications

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABAA Receptor Trafficking

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABAA Receptor Trafficking

The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5

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Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABA_A Receptor Trafficking

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABA_A Receptor Trafficking