Enhanced expression of uridine diphosphate–N-acetylglucosaminyl transferase (OGT) in a stable, tetracycline-inducible HeLa cell line using histone deacetylase inhibitors: kinetics of cytosolic OGT accumulation and nuclear translocation

Marshall, Stephen; Duong, Trung; Wu, Tong; Hering, Michelle A; Yada, Jason; Higgins, Sarah J.; Orbus, Ryan J; Yan, Zhao; Rumberger, John M.

doi:10.1016/s0003-2697(03)00329-4

Cited by 15 publications

(18 citation statements)

References 17 publications

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“…Based on direct evidence of H3K9 acetylation and the use of TSA, we concluded that one signaling mechanism for the induction of IL-10RA was HDACi, a function for which butyrate is well established (19). It is interesting to note that propionate and acetate also increased IL-10RA mRNA, which could be due to their ability to inhibit HDACs to a lesser degree, although propionate and acetate are far less potent than butyrate as HDAC inhibitors (44, 45). We did not find an induction of IL-10RA with hypoxia treatment nor HIF stabilization (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor–Dependent Repression of Claudin-2

Zheng

Kelly

Battista

et al. 2017

The Journal of Immunology

396

260

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Commensal interactions between the enteric microbiota and distal intestine play important roles in regulating human health. Short-chain fatty acids (SCFAs), such as butyrate, produced through anaerobic microbial metabolism represent a major energy source for the host colonic epithelium and enhance epithelial barrier function through unclear mechanisms. Separate studies revealed that the epithelial anti-inflammatory interleukin-10 receptor α-subunit (IL-10RA) is also important for barrier formation. Based on these findings, we examined if SCFAs promote epithelial barrier through IL-10RA-dependent mechanisms. Using human intestinal epithelial cells (IECs), we discovered that SCFAs, particularly butyrate, enhanced IEC barrier formation, induced IL10RA mRNA, IL-10RA protein, and transactivation through activated Stat3 and HDAC inhibition. Loss and gain of IL10RA expression directly correlates with IEC barrier formation and butyrate represses permeability-promoting claudin-2 (Cldn2) tight-junction protein expression through an IL-10RA-dependent mechanism. Our findings provide a novel mechanism by which microbial-derived butyrate promotes barrier through IL-10RA-dependent repression of Cldn2.

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Section: Discussionmentioning

confidence: 99%

Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor–Dependent Repression of Claudin-2

Zheng

Kelly

Battista

et al. 2017

The Journal of Immunology

396

260

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“…Techniques such as over expression of OGT (Zachara et al 2004b), OGlcNAcase (Slawson et al 2005), and GFAT (Chen et al 1997;Marshall et al 2004;James et al 2000) by both transient transfection and viral transduction have been successful, as has reducing the expression of these enzymes using RNA interference (Zachara et al 2004b;Ngoh et al 2009a;Hsieh et al 2012). OGT has also been overexpressed using a tetracycline-inducible OGT stably expressed in HeLa cells, although for effective overexpression a histone deacetylase inhibitor was included with the tetracycline for appropriate regulation of OGT (Marshall et al 2003).…”

Section: In Vitro and In Vivo Modulation Of O-glcnac Levelsmentioning

confidence: 99%

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Groves

Lee

Yildirir

et al. 2013

Cell Stress and Chaperones

120

112

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O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) is a ubiquitous and dynamic post-translational modification known to modify over 3,000 nuclear, cytoplasmic, and mitochondrial eukaryotic proteins. Addition of O-GlcNAc to proteins is catalyzed by the O-GlcNAc transferase and is removed by a neutral-N-acetyl-β-glucosaminidase (OGlcNAcase). O-GlcNAc is thought to regulate proteins in a manner analogous to protein phosphorylation, and the cycling of this carbohydrate modification regulates many cellular functions such as the cellular stress response. Diverse forms of cellular stress and tissue injury result in enhanced O-GlcNAc modification, or O-GlcNAcylation, of numerous intracellular proteins. Stress-induced OGlcNAcylation appears to promote cell/tissue survival by regulating a multitude of biological processes including: the phosphoinositide 3-kinase/Akt pathway, heat shock protein expression, calcium homeostasis, levels of reactive oxygen species, ER stress, protein stability, mitochondrial dynamics, and inflammation. Here, we will discuss the regulation of these processes by O-GlcNAc and the impact of such regulation on survival in models of ischemia reperfusion injury and trauma hemorrhage. We will also discuss the misregulation of O-GlcNAc in diseases commonly associated with the stress response, namely Alzheimer's and Parkinson's diseases. Finally, we will highlight recent advancements in the tools and technologies used to study the O-GlcNAc modification.

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“…SCFA have a number of effects on cells, many of which, especially those of butyrate, are mediated through inhibition of histone deacetylases (HDACs) [12][13][14]. HDACs are involved in the pathogenesis of diabetes and are currently of interest as targets for the treatment of several diseases including diabetes and cancer [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Butyrate and other Short-Chain Fatty Acids Increase the Rate of Lipolysis in 3T3-L1 Adipocytes

Rumberger

Arch

Green

2014

Preprint

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We determined the effect of butyrate and other short-chain fatty acids (SCFA) on rates of lipolysis in 3T3-L1 adipocytes. Prolonged treatment with butyrate (5 mM) increased the rate of lipolysis approximately 2-3-fold. Aminobutyric acid and acetate had little or no effect on lipolysis, however propionate stimulated lipolysis, suggesting that butyrate and propionate act through their shared activity as histone deacetylase (HDAC) inhibitors. Consistent with this, the HDAC inhibitor trichostatin A (1 μM) also stimulated lipolysis to a similar extent as did butyrate. Western blot data suggested that neither mitogen-activated protein kinase (MAPK) activation nor perilipin down-regulation are necessary for SCFA-induced lipolysis. Stimulation of lipolysis with butyrate and trichostatin A was glucose-dependent. Changes in AMP-activated protein kinase (AMPK) phosphorylation mediated by glucose were independent of changes in rates of lipolysis. The glycolytic inhibitor iodoacetate prevented both butyrate- and Tumor necrosis factor-alpha-(TNF-α ) mediated increases in rates of lipolysis indicating glucose metabolism is required. However, unlike TNF-α - , butyrate-stimulated lipolysis was not associated with increased lactate release or inhibited by activation of pyruvate dehydrogenase (PDH) with dichloroacetate. These data demonstrate an important relationship between lipolytic activity and reported HDAC inhibitory activity of butyrate, other short-chain fatty acids and trichostatin A. Given that HDAC inhibitors are presently being evaluated for the treatment of diabetes and other disorders, more work will be essential to determine if these effects on lipolysis are due to inhibition of HDAC.

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Enhanced expression of uridine diphosphate–N-acetylglucosaminyl transferase (OGT) in a stable, tetracycline-inducible HeLa cell line using histone deacetylase inhibitors: kinetics of cytosolic OGT accumulation and nuclear translocation

Cited by 15 publications

References 17 publications

Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor–Dependent Repression of Claudin-2

Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor–Dependent Repression of Claudin-2

Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

Butyrate and other Short-Chain Fatty Acids Increase the Rate of Lipolysis in 3T3-L1 Adipocytes

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