Opposite effects of sodium butyrate on CCK mRNA and CCK peptide levels in RIN cells

The effects of the differentiation-inducing agent sodium butyrate on cholecystokinin (CCK) expression was investigated in the pancreatic islet tumor cell line RIN 1056E, which contains high levels of CCK-like immunoreactivity (CCK-LI). Exposure to butyrate for 24 h dose-dependently inhibited cell proliferation and increased the cell content in CCK-LI over the concentration range 0.1–8 mM. With 2 mM butyrate, cell proliferation was decreased by 50% and CCK-LI content was increased by 300%, whereas the level of steady-state CCK mRNA was reduced by 75%. Cycloheximide (10 μg/mL) abolished the sodium butyrate-induced increase in CCK-LI content. This article reports the novel finding that butyrate exerts opposite effects on CCK mRNA and immunoreactivity. The butyrate-induced increase in cellular CCK-LI content is entirely dependent on continuing protein synthesis.     

丁酸对人结肠癌细胞尿激酶型纤溶酶原激活剂及受体表达的影响

目的探讨丁酸对人结肠癌细胞尿激酶型纤溶酶原激活剂(u-PA)及其受体(u-PAR)表达的影响。方法将人传代结肠癌细胞株SW1116接种于不含或含不同浓度丁酸(2、3、4、7、10mmol／L)的培养基中，培养6、24、48、72h后，收集细胞用ELISA法测定胞质中u-PA和u-PAR的表达情况。结果随着培养基中丁酸浓度的增加和培养时间的延长，经丁酸处理的SW1116细胞表达的u-PA和u-PAR与对照组相比显著减少，当丁酸浓度≥4mmol／L和培养时问≥48h时，两者表达不再增加，反而呈逐步下降趋势。结论丁酸可抑制SW1116细胞u-PA和u-PAR表达。     

Melatonin and its precursors in Y79 human retinoblastoma cells: effect of sodium butyrate

We studied the release of melatonin and the production of its precursors, 5-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for 3 days. This protocol dramatically increased the release of melatonin and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine (10 microM) or L-DOPA (100 microM) markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation (e.g. treatment with sodium butyrate) can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 cells. The inhibition of melatonin release by dopamine supports the hypothesis that in these cells, melatonin and dopamine are components of a retinal feedback loop.     

Exposure to sodium butyrate leads to functional downregulation of calcium-activated potassium channels in human airway epithelial cells

Cystic fibrosis (CF) is caused by genetic mutations that lead to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl^- channel. The most common mutation, ΔF508, causes inefficient trafficking of mutant CFTR protein from the endoplasmic reticulum to the cell membrane. Therapeutic efforts have been aimed at increasing the level of ΔF508-CFTR protein in the membrane using agents such as sodium butyrate. In this study, we investigated the effects of culturing a human airway epithelial cell line, Calu-3, in the presence of 5 mM sodium butyrate. Within 24 h, butyrate exposure caused a significant decrease in the basal, as well as Ca²⁺-activated, anion secretion by Calu-3 cell monolayers, determined by the change in transepithelial short-circuit current in response to the Ca²⁺-elevating agent thapsigargin. The secretory response to 1-ethyl-2-benzimidazolinone, an activator of the basolateral Ca²⁺-activated K⁺ channel KCNN4, was similarly reduced by butyrate treatment. Quantitative PCR revealed that these functional effects were associated with dramatic decreases in mRNA for both KCNN4 and CFTR. Furthermore, the KCNQ1 K⁺ channel was upregulated after butyrate treatment. We suggest that prolonged exposure to sodium butyrate downregulates the expression of both KCNN4 and CFTR, leading to a functional loss of Ca²⁺-activated anion secretion. Thus, butyrate may inhibit, rather than stimulate, the anion secretory capacity of human epithelial cells that express wild-type CFTR, particularly in tissues that normally exhibit robust Ca²⁺-activated secretion.     

Electrophysiological correlates of adjustment process in anchoring effects

Dibutyryl cyclic AMP (dbcAMP) and retinoic acid (RA) have been demonstrated to be the inducers of morphological differentiation in SH-SY5Y cells, a human catecholaminergic neuroblastoma cell line. However, it remains unclear whether morphologically differentiated SH-SY5Y cells by these compounds acquire catecholaminergic properties. We focused on the alteration of tyrosine hydroxylase (TH) expression and intracellular content of noradrenaline (NA) as the indicators of functional differentiation. Three days treatment with dbcAMP (1mM) and RA (10muM) induced morphological changes and an increase of TH-positive cells using immunocytochemical analysis in SH-SY5Y cells. The percentage of TH-expressing cells in dbcAMP (1mM) treatment was larger than that in RA (10muM) treatment. In addition, dbcAMP increased intracellular NA content, whereas RA did not. The dbcAMP-induced increase in TH-expressing cells is partially inhibited by KT5720, a protein kinase A (PKA) inhibitor. We also investigated the effect of butyrate on SH-SY5Y cells, because dbcAMP is enzymatically degraded by intracellular esterase, thereby resulting in the formation of butyrate. Butyrate induced the increase of NA content at lower concentrations than dbcAMP, although the increase in TH-expressing cells by butyrate was smaller than that by dbcAMP. The dbcAMP (1mM)- and butyrate (0.3mM)-induced increase in NA content was completely suppressed by alpha-methyl-p-tyrosine (1mM), an inhibitor of TH. These results suggest that dbcAMP induces differentiation into the noradrenergic phenotype through both PKA activation and butyrate.     

The effect of polyethylene glycol and butyrate on anastomotic healing in the rat colon

Background The use of mechanical bowel preparation is much debated. Methods We evaluated the effects of polyethylene glycol (PEG), with or without a single dose of 3.0 mmol butyrate (BUT), on the bursting pressure (BP) of an intact colon segment and a colon anastomosis in rats. Also, histopathologic damage was studied. Results In rats without colectomy, the mean BP was 159.2 mmHg (SD=18.9) after PEG treatment and 116.7 mmHg (SD=27.5) in controls (p=0.001). In rats with colectomy, the mean BP was 90.4 mmHg (SD=45.9) in the PEG group, 108.0 mmHg (SD=31.9) in the BUT group, and 102.7 mmHg (SD=44.7) in controls (p=0.44). No significant differences in histopathologic scores were observed between rats treated with PEG and controls. Conclusions PEG does not interfere with anastomotic healing in rats as measured by BP. No benefit of a single dose of butyrate was observed. An erratum to this article is available at .     

丁酸对人牙周膜细胞增殖的影响

目的探讨丁酸对牙周膜细胞增殖的影响.方法用含不同浓度丁酸(0、2、4、8 mmol/L)的培养液培养人牙周膜细胞,通过MTT法测定其生长与增殖.结果人牙周膜细胞进入指数生长期后,丁酸以剂量依赖的方式抑制人牙周膜细胞的增殖.结论龈下厌氧菌代谢生成的丁酸可能通过抑制人牙周膜细胞的增殖,进而影响牙周膜的改建和更新,促进牙周袋形成和牙周组织破坏.     

丁酸氢化可的松乳膏联合类人胶原蛋白敷料对湿疹患儿EASI、IDQOL评分的影响

目的观察丁酸氢化可的松乳膏联合类人胶原蛋白敷料对湿疹患儿湿疹面积及严重程度指数(EASI)、婴儿湿疹皮肤生活指数(IDQOL)评分的影响。方法以2017年10月至2019年10月接收的146例湿疹患儿为研究对象,使用区组随机化分组将其分为甲组(n=73)和乙组(n=73)。乙组使用丁酸氢化可的松乳膏,甲组在其基础上联合类人胶原蛋白敷料。治疗2周后,比较两组疗效,对比治疗前、治疗2周后两组湿疹严重程度[湿疹面积及严重程度评分(EASI)]、生活指数[婴儿湿疹皮肤生活指数(IDQOL)]变化,统计治疗2周内两组药物不良反应发生率。结果治疗2周后,甲组治疗有效率显著高于乙组(P<0.05);两组患儿EASI、IDQOL评分较治疗前均有显著降低(P<0.05),且甲组明显低于乙组(P<0.05);治疗2周内,两组药物不良反应发生率无显著差异(P>0.05)。结论丁酸氢化可的松乳膏联合类人胶原蛋白敷料对湿疹患儿有较高的疗效,可改善患儿湿疹症状,且药物安全性较高,具有较高临床应用价值。