Concomitant Changes in Polyamine Pools and DNA Methylation during Growth Inhibition of Human Colonic Cancer Cells

Duranton, B; Keith, Gérard; Gossé, Francine; Bergmann, Christian; Schleiffer, R.; Raul, Françis

doi:10.1006/excr.1998.4148

Cited by 25 publications

(9 citation statements)

References 22 publications

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“…5C; Supplemental Fig. 3D shows all significant gene categories; Duranton et al 1998;Wang et al 2012;Noah and Shroyer 2013). Finally, 523 out of 3758 ''differentiation-induced'' genes, highly expressed in villous cells, showed decreased methylation after differentiation and included enterocyte-specific genes such as Lct, Alpi, and Krt20 (Fig.…”

Section: Dmrs (Supplementalmentioning

confidence: 96%

DNA methylation is required for the control of stem cell differentiation in the small intestine

et al. 2014

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The mammalian intestinal epithelium has a unique organization in which crypts harboring stem cells produce progenitors and finally clonal populations of differentiated cells. Remarkably, the epithelium is replaced every 3-5 d throughout adult life. Disrupted maintenance of the intricate balance of proliferation and differentiation leads to loss of epithelial integrity or barrier function or to cancer. There is a tight correlation between the epigenetic status of genes and expression changes during differentiation; however, the mechanism of how changes in DNA methylation direct gene expression and the progression from stem cells to their differentiated descendants is unclear. Using conditional gene ablation of the maintenance methyltransferase Dnmt1, we demonstrate that reducing DNA methylation causes intestinal crypt expansion in vivo. Determination of the base-resolution DNA methylome in intestinal stem cells and their differentiated descendants shows that DNA methylation is dynamic at enhancers, which are often associated with genes important for both stem cell maintenance and differentiation. We establish that the loss of DNA methylation at intestinal stem cell gene enhancers causes inappropriate gene expression and delayed differentiation.

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Section: Dmrs (Supplementalmentioning

confidence: 96%

DNA methylation is required for the control of stem cell differentiation in the small intestine

et al. 2014

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“…Recently, Remely and coworkers demonstrated that distinct composition of gut microbiota producing different SCFAs may affect epigenetic gene regulation in obesity and T2D [15]. In addition, partial prevention of obesity through histone acetylation by SCFAs was reported by Duranton and colleagues more than ten years ago [16]. These beneficial effects of SCFAs were not only related to their property as histone deacetylase inhibitors, but also related to their activation of the transmembrane cognate G protein-coupled receptors [17].…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Gut Microbiota Short-Chain Fatty Acids as Key Pathophysiological Molecules Improving Diabetes

Puddu

Sanguineti

Montecucco

et al. 2014

Mediators of Inflammation

250

203

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In type 2 diabetes, hyperglycemia, insulin resistance, increased inflammation, and oxidative stress were shown to be associated with the progressive deterioration of beta-cell function and mass. Short-chain fatty acids (SCFAs) are organic fatty acids produced in the distal gut by bacterial fermentation of macrofibrous material that might improve type 2 diabetes features. Their main beneficial activities were identified in the decrease of serum levels of glucose, insulin resistance as well as inflammation, and increase in protective Glucagon-like peptide-1 (GLP-1) secretion. In this review, we updated evidence on the effects of SCFAs potentially improving metabolic control in type 2 diabetes.

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“…The polyamines putrescine (Put), spermidine (Spd), spermine (Spm), and their acetylated derivatives, are a prerequisite for cellular metabolism (Pegg 1988). A role of polyamines for inducing a proliferative response, or to maintain cell differentiation, has been demonstrated for a variety of cell types (Verma & Sunkara 1982;Frostesjo et al 1997;Duranton et al 1998). It has also been shown that polyamines are essential for hepatic regeneration in that inhibition of their synthesis by chemical agents significantly impairs regenerative activity after partial hepatectomy (Diehl et al 1990;Luk 1986).…”

Section: Introductionmentioning

confidence: 99%

Collagen sandwich culture affects intracellular polyamine levels of human hepatocytes

Weiss

Jahn²,

Cetto

et al. 2002

Cell Proliferation

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Extracellular matrices, like collagen layers, play an important role in preventing dedifferentiation of hepatocytes in long-term culture experiments. It has also been shown that polyamines are crucial for cell growth and liver differentiation - regeneration. Primary cultured hepatocytes with their low mitotic activity might be a valuable tool in studying the role of polyamines in differentiation. Here, our goal was to investigate whether an extracellular cell culture matrix can influence intracellular polyamine levels in human hepatocytes during long-term culture. Primary human hepatocytes were isolated from surgical tissue resections and were maintained either in single collagen (SG) or double collagen gel (DG) layer (sandwich) culture systems. Cell viability and function were examined and intracellular polyamine levels were measured using a highly sensitive high performance liquid chromatography (HPLC) method. Hepatocytes showed high viability in both culture systems used, but albumin secretion was diminished in SG cultured hepatocytes after 14 days. In general, total intracellular polyamine levels of hepatocytes decreased markedly in both SG and DG within the first days of culture, but remained constant until day 21 with a SG/DG ratio of about 1.4. Individual polyamines levels were dependent on the culture time and system, where spermine decreased and putrescine increased in both SG and DG over time (day 14), but spermidine increased only in DG. Our results suggest that polyamine levels, in particular putrescine, might be important regulators of hepatocyte specific function in vitro and therefore serve as a marker of differentiation for cultivated human hepatocytes.

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Concomitant Changes in Polyamine Pools and DNA Methylation during Growth Inhibition of Human Colonic Cancer Cells

Cited by 25 publications

References 22 publications

DNA methylation is required for the control of stem cell differentiation in the small intestine

DNA methylation is required for the control of stem cell differentiation in the small intestine

Evidence for the Gut Microbiota Short-Chain Fatty Acids as Key Pathophysiological Molecules Improving Diabetes

Collagen sandwich culture affects intracellular polyamine levels of human hepatocytes

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