Butyrate and the Colonocyte

Velázquez, Omaida C.; Lederer, Howard M.; Rombeau, John L.

doi:10.1007/978-1-4615-5967-2_14

Cited by 177 publications

(42 citation statements)

References 47 publications

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“…Na ϩ /H ϩ exchange, particularly that mediated by NHE1, plays a key role in catalyzing the removal of protons in colon epithelium (75)(76)(77). In the present study, we describe two different regulatory mechanisms resulting in the stimulation of NHE1 activity in colonocytes.…”

Section: Discussionmentioning

confidence: 82%

Extracellular Zinc Triggers ERK-dependent Activation of Na+/H+ Exchange in Colonocytes Mediated by the Zinc-sensing Receptor

Azriel-Tamir

Sharir²,

Schwartz

et al. 2004

Journal of Biological Chemistry

120

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Extracellular zinc promotes cell proliferation and its deficiency leads to impairment of this process, which is particularly important in epithelial cells. We have recently characterized a zinc-sensing receptor (ZnR) linking extracellular zinc to intracellular release of calcium. In the present study, we addressed the role of extracellular zinc, acting via the ZnR, in regulating the MAP kinase pathway and Na Arrested cell proliferation is a hallmark of zinc deficiency. This is particularly true in gastrointestinal cells (1-4), where insufficient dietary zinc attenuates the renewal of the epithelium leading to severe diarrhea (1). Extracellular zinc has been shown to regulate cell proliferation via the MAP 1 kinase pathway in several cell types (5-7). Although the mitogenic and anti-apoptotic effects of zinc are well recognized (8, 9), and the treatment of severe diarrhea by addition of dietary zinc is common, the direct link between this ion and the cellular mechanisms regulating proliferation is not well understood. It has been suggested that a decrease in intracellular zinc may lead directly to a reduction in activity of various metalloenzymes involved in transcription and cell metabolism (1, 10). Several studies, however, indicate that extracellular zinc acts as a signaling molecule. In tracheal cells, for example, extracellular zinc, through activation of Src, leads to transactivation of EGFR and subsequently to activation of ERK1/2 (11). In fibroblasts, extracellular zinc has been shown to trigger the activation of the PI3K pathway, subsequently leading to the activation of AKT and the S6 kinase (12). The signaling pathways linking extracellular zinc to these proteins and to subsequent regulation of cellular ion, pH or volume homeostasis, however, remain poorly understood.We have recently identified and characterized an extracellular zinc-sensing receptor (ZnR) that triggers, upon exposure to extracellular zinc, the release of Ca 2ϩ from intracellular stores by activation of the IP 3 pathway (13). The pharmacological profile of the calcium response triggered by the ZnR, particularly its sensitivity to the PLC inhibitor, U73122, and the inhibitory effect of the IP 3 receptor blocker, 2-APB, indicates that the ZnR is a G q -coupled receptor (GPCR). Both the G␣ and the G␤␥ dimer of various GPCRs have been linked to activation of the MAP kinase via multiple intracellular pathways (14 -16). In intestinal cells, furthermore, the muscarinic receptor has been shown to play a key role in promoting ion transport through activation of MAP and PI 3-kinase signal transduction (17,18). A role for the ZnR in activation of the MAP kinase pathway is demonstrated in this work.The ZnR was initially characterized in the colonocytic cell line, HT29, where a robust calcium signal was generated following activation of the receptor by changes in the concentration of extracellular Zn 2ϩ (13). Importantly, the Ca 2ϩ response induced by the ZnR in HT29 cells is triggered by ϳ80 M zinc, i.e. within the physiological range of zinc conc...

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Section: Discussionmentioning

confidence: 82%

Extracellular Zinc Triggers ERK-dependent Activation of Na+/H+ Exchange in Colonocytes Mediated by the Zinc-sensing Receptor

Azriel-Tamir

Sharir²,

Schwartz

et al. 2004

Journal of Biological Chemistry

120

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“…In addition to its well-known function as an essential energy source for colonocytes and growth inhibitory effects on cancer cells, NaB has anti-inflammatory and immunosuppressive effects in vitro and in vivo (Velazquez et al, 1997;Andoh et al, 1999;Inan et al, 2000;Saemann et al, 2000). Several proinflammatory cytokines, including TNF and IL-1, have been shown to activate NF-kB (Pahl, 1999).…”

Section: Discussionmentioning

confidence: 99%

Expression profiling of sodium butyrate (NaB)-treated cells: identification of regulation of genes related to cytokine signaling and cancer metastasis by NaB

et al. 2004

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Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (NaB), a short chain fatty acid, is a HDAC inhibitor and is produced in the colonic lumen as a consequence of microbial degradation of dietary fibers. In order to dissect out the mechanism of NaB-induced growth inhibition of cancer cells, we carried out expression profiling of a human lung carcinoma cell line (H460) treated with NaB using a cDNA microarray. Of the total 1728 genes analysed, there were 32 genes with a mean expression value of 2.0-fold and higher and 66 genes with a mean expression value 3.0-fold and lower in NaBtreated cells. For a few selected genes, we demonstrate that their expression pattern by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis is matching with the results obtained by microarray analysis. Closer view at the expression profile of NaBtreated cells revealed the downregulation of a total of 16 genes associated with cytokine signaling, in particular, interferon c (IFNc) pathway. In good correlation, NaBpretreated cells failed to induce interferon regulatory factor 1, an INFc target gene, efficiently upon IFNc addition. These results suggest that NaB inhibits proinflammatory cytokine signaling pathway, thus providing proof of mechanism for its anti-inflammatory activity. We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis. Upregulation of metastatic suppressor Kangai 1 (KAI1) by NaB in a time-dependent manner was confirmed by RT-PCR analysis. The differential regulation of metastasis-associated genes by NaB provides explanation for the antiinvasive properties of NaB. Therefore, our study presents new evidence for pathways regulated by NaB, thus providing evidence for the mechanism behind antiinflammatory and antimetastatic activities of NaB.

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“…Short chain fatty acids benefit the colonic mucosa in a number of ways (1)(2)(3)(4)(5). Colonocytes utilize short chain fatty acids as their primary energy source, and evidence has been obtained that they undergo apoptosis in its absence (2,(5)(6)(7).…”

mentioning

confidence: 99%

Butyrate Suppression of Colonocyte NF-κB Activation and Cellular Proteasome Activity

Yin

Laevsky

Giardina

2001

Journal of Biological Chemistry

244

145

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Butyrate and the Colonocyte

Cited by 177 publications

References 47 publications

Extracellular Zinc Triggers ERK-dependent Activation of Na+/H+ Exchange in Colonocytes Mediated by the Zinc-sensing Receptor

Extracellular Zinc Triggers ERK-dependent Activation of Na+/H+ Exchange in Colonocytes Mediated by the Zinc-sensing Receptor

Expression profiling of sodium butyrate (NaB)-treated cells: identification of regulation of genes related to cytokine signaling and cancer metastasis by NaB

Butyrate Suppression of Colonocyte NF-κB Activation and Cellular Proteasome Activity

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