Role of polyamines in gastrointestinal mucosal growth

McCormack, Shirley A.; Johnson, L. R.

doi:10.1152/ajpgi.1991.260.6.g795

Cited by 113 publications

(112 citation statements)

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“…Several mechanisms for controlling this adaptive response have been postulated, including the effect of bacterial metabolic products, physical characteristics of luminal content, and systemic factors (hormonal and neural) (22,33,55). The evidence from different studies regarding the principle factor(s) involved is often conflicting, suggesting that there are multiple factors that interact to control colonic mucosal growth characteristics.…”

Section: Introductionmentioning

confidence: 99%

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The Interactions of Diet and Colonic Microflora in Regulating Colonic Mucosal Growth

et al. 1996

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The colonic mucosa can adapt its growth to alterations in diet. Metabolites from colonic microflora are frequently implicated as the primary factor in mediating the colonic mucosal response to diet; however, there is also evidence indicating that diet may have a direct effect in mediating this response. The aim of this study was to determine the role of diet, microflora, and microflora metabolites in altering the growth of the colonic mucosa. Two 28-day feeding studies were conducted using Sprague-Dawley rats. The first study compared the growth of the colonic mucosa in germ-free and conventional rats fed 6 different diets. The second study compared the growth of the colonic mucosa to the concentration of bacterial-derived short-chain fatty acids (SCFAs), bile acids, and ammonia. The diets that were fed consisted of (1) AIN-76a diet without dietary fiber; (2) standard AIN-76a diet, which contained 5% cellulose; (3) AIN-76a diet with 5% guar gum; (4) a "Western" human diet with 20% fat and 10% cellulose; (5) AIN-76a diet formulated to mimic Diet 4 in fat content but with 2.5% cellulose; and (6) Purina Rodent Chow. Quantitative volumetric and stereologic analysis was used to assess changes in total colonic mucosal volume as a measure of mucosal growth. In germ-free rats, Diets 2-4 and 6 induced a significant increase (18-38%) in mucosal volume compared to Diet 1. In conventional animals, only Diets 4 and 6 induced a significant increase (up to 63%) in mucosal volume compared to Diet 1. Relative to the germ-free animals, only conventional animals on Diets 4 and 6 had an increase in mucosal volume. The increases in mucosal volume in Diets 4 and 6 were not consistently associated with increased SCFAs, ammonia, or bile acids. There was a wide range in the colonic concentrations of SCFAs (2-fold), ammonia (6-fold), and bile acids (10-fold). The presence of colonic microflora in and of itself does not lead to enhanced colonic mucosal growth. Rather, there are unique interactions between specific types of diet and microflora that lead to a growth-promoting effect. This effect could not be explained by alterations in the concentration of SCFAs, ammonia, or bile acids in colonic contents.

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Section: Introductionmentioning

confidence: 99%

“…Other studies, however, have failed to show that high-fat diets elevate colonic bile acid concentration (9,17) in rats or increase epithelial cell proliferation in the colon (26,27,31,52). Other bacterial metabolites, such as ammonia and polyamines, have also been implicated in influencing mucosal growth (33,56).…”

Section: Introductionmentioning

confidence: 99%

The Interactions of Diet and Colonic Microflora in Regulating Colonic Mucosal Growth

et al. 1996

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“…The regulation of cellular polyamines is thought to be a central convergence point for the multiple signaling pathways driving epithelial cell function. We (6, 8 -14) and others (1,5,15) have demonstrated that normal epithelial cell proliferation in the intestinal mucosa depends on the supply of polyamines to the dividing cells and that decreasing cellular polyamines inhibits epithelial cell proliferation by stabilizing the mRNAs that encode nucleophosmin (NPM), 3 p53, and other growth-inhibiting factors. However, the exact mechanisms whereby polyamine depletion stabilizes NPM and p53 mRNAs remain elusive.…”

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confidence: 99%

Polyamine Depletion Increases Cytoplasmic Levels of RNA-binding Protein HuR Leading to Stabilization of Nucleophosmin and p53 mRNAs

Zou¹,

Mazan-Mamczarz

Rao³

et al. 2006

Journal of Biological Chemistry

114

167

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Polyamines are essential for maintaining normal intestinal epithelial integrity, an effect that relies, at least in part, on their ability to keep low levels of nucleophosmin (NPM) and p53 mRNAs. The RNA-binding protein HuR associates with the p53 mRNA, as reported previously, and with the NPM mRNA, computationally predicted to be a target of HuR. Here, we show that HuR binds the NPM and p53 3-untranslated regions and stabilizes these mRNAs in polyaminedepleted intestinal epithelial cells. Depletion of cellular polyamines by inhibiting ornithine decarboxylase with ␣-difluoromethylornithine dramatically enhanced the cytoplasmic abundance of HuR, whereas ectopic ornithine decarboxylase overexpression decreased cytoplasmic HuR; neither intervention changed whole-cell HuR levels. HuR was found to specifically bind the 3-untranslated regions of NPN and p53 mRNAs. HuR silencing rendered the NPM and p53 mRNAs unstable and prevented increases in NPM and p53 mRNA and protein in polyamine-deficient cells. These results indicate that polyamines modulate cytoplasmic HuR levels in intestinal epithelial cells, in turn controlling the stability of the NPM and p53 mRNAs and influencing NPM and p53 protein levels.

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“…In addition, probiotic products are important mediators of cell growth and differentiation and prevent lipid peroxidation in liver microsomes. [25,26] Our findings suggest that dual-coated and uncoated probiotic supplements may exhibit hepatoprotective effects by affecting the oxidative stress levels and TNF-a.…”

Section: Parametersmentioning

confidence: 80%

Hepatoprotective effects of dual-coated and uncoated mixture of probiotics in rats

Park

Lee

Kim

et al. 2015

Biotechnology & Biotechnological Equipment

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Probiotics have been used for the treatment of various disorders or as alternative therapies. The stability of dual-coated probiotics is increased in the gastrointestinal environment. The aim of the present study was to evaluate the hepatoprotective effects of dual-coated and uncoated probiotic supplements, following liver injury. Albino Wistar rats were orally treated with probiotics daily and carbon tetrachloride (CCl 4 ) was administered on the seventh and eighth days to induce acute liver damage. Hepatoprotective effects were determined by assessment of serum glutamicÀoxaloacetic transaminase (SGOT) and serum glutamicÀpyruvic transaminase (SGPT) activities, as well as by histopathological examination. The CCl 4 -treated control group showed increased SGOT and SGPT activities as compared with the normal control group. However, treatment with probiotics reduced SGOT and SGPT activities, following CCl 4 administration. Animals treated with probiotics showed reduced liver weight than that in the standard CCl 4 group which did not receive probiotics. Histopathological analysis showed that administration of probiotics minimized liver damage by reducing the level of morphological changes and necrosis. Therefore, probiotics may be effective hepatoprotective agents and should be considered useful for the treatment and prevention of hepatic disorders.

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Role of polyamines in gastrointestinal mucosal growth

Cited by 113 publications

References 0 publications

The Interactions of Diet and Colonic Microflora in Regulating Colonic Mucosal Growth

The Interactions of Diet and Colonic Microflora in Regulating Colonic Mucosal Growth

Polyamine Depletion Increases Cytoplasmic Levels of RNA-binding Protein HuR Leading to Stabilization of Nucleophosmin and p53 mRNAs

Hepatoprotective effects of dual-coated and uncoated mixture of probiotics in rats

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