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Mingmin Chen,
Jeppe Praetorius,
Wen Zheng,
Fang Xiao,
Brigitte Riederer,
Anurag Kumar Singh,
Nicole Stieger, Jian Wang,
Gary E Shull,
Christian Aalkjaer,
Ursula Seidler
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ABSTRACT: Duodenocyte pHi control and HCO3 − secretion protects the proximal duodenum against damage by gastric acid. The molecular details of duodenocyte pH control are not well understood. A selective duodenal expression (within the upper GI tract) has been reported for the electroneutral Na+:HCO3 − cotransporter NBCn1 (Slc4a7). We aimed to determine the role of NBCn1 and NBCe2 in duodenocyte intracellular pH regulation as well as basal and agonist-stimulated duodenal bicarbonate secretion (JHCO3 −), exploiting mouse models of genetic slc4a7 and slc4a5 disruption. Basal and forskolin (FSK)-stimulated JHCO3 − was measured by single-pass perfusion in the duodenum of slc4a7−/− and slc4a7+/+ as well as slc4a5−/− and slc4a5+/+ mice in vivo, and by pH-stat titration in isolated duodenal mucosa in vitro. Duodenocyte HCO3 − uptake rates were fluorometrically assessed after acidification of intact villi and of isolated duodenocytes. Slc4a7−/− mice displayed significantly lower basal and FSK-stimulated duodenal HCO3 − secretion than slc4a7+/+ littermates in vivo. FSK-stimulated HCO3 − secretion was significantly reduced in slc4a7−/− isolated duodenal mucosa. Na+- and HCO3 −-dependent base uptake rates were significantly decreased in slc4a7−/− compared with slc4a7+/+ villus duodenocytes when measured in intact villi. Carbonic anhydrase (CA)-mediated CO2 hydration played no apparent role as a HCO3 − supply mechanism for basal or FSK-stimulated secretion in the slc4a7+/+ duodenum, but was an important alternative HCO3 − supply mechanism in the slc4a7−/− duodenum. NBCe2 (Slc4a5) displayed markedly lower duodenal mRNA expression levels, and its disruption did not interfere with duodenal HCO3 − secretion. The electroneutral Na+:HCO3 − cotransporter NBCn1 (slc4a7) is a major duodenal HCO3 − importer that supplies HCO3 − during basal and FSK-stimulated HCO3 − secretion.
The Journal of Physiology 05/2012; 590(Pt 14):3317-33. · 4.72 Impact Factor
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ABSTRACT: The epoxy resin matrix of carbon fiber (CF)-reinforced epoxy composites was modified with novolac resin (NR) to improve the matrix-dominated mechanical properties of composites. Flexural strength, interlaminar shear strength (ILSS), and impact strength were measured with unfilled, 7 wt% NR, 13 wt% NR, and 18 wt% NR filled to epoxy to identify the effect of adding NR on the mechanical properties of composites. The results showed that both interfacial and impact properties of composites were improved except for flexural property. The largest improvement in ILSS and impact strength were obtained with 13 wt% loading of NR. ILSS and impact strength were improved by 7.3% and 38.6%, respectively, compared with the composite without NR. The fracture and surface morphologies of the composite specimens were characterized by scanning electron microscopy. Intimate bonding of the fibers and the matrix was evident with the content of 7–13 wt% NR range. Decrease of crosslinking density and formation of NR transition layer were deduced with adding NR. POLYM. COMPOS., 2011. © 2010 Society of Plastics Engineers
Polymer Composites 11/2010; 32(2):227 - 235. · 1.23 Impact Factor
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Mingmin Chen,
Anurag Singh,
Fang Xiao,
Ulrike Dringenberg, Jian Wang,
Regina Engelhardt,
Sunil Yeruva,
Isabel Rubio-Aliaga,
Anna-Maria Nässl,
Gabor Kottra,
Hannelore Daniel,
Ursula Seidler
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ABSTRACT: PEPT1 function in mouse intestine has not been assessed by means of electrophysiology and methods to assess its role in intracellular pH and fluid homeostasis. Therefore, the effects of the dipeptide glycilsarcosin (Gly-Sar) on jejunal fluid absorption and villous enterocyte intracellular pH (pH(i)) in vivo, as well as on enterocyte[(14)C]Gly-Sar uptake, short-circuit current (I(sc)) response, and enterocyte pH(i) in vitro were determined in wild-type and PEPT1-deficient mice and in mice lacking PEPT1. Immunohistochemistry for PEPT1 failed to detect any protein in enterocyte apical membranes in Slc15a1(-/-) animals. Saturable Gly-Sar uptake in Slc15a1(-/-) everted sac preparations was no longer detectable. Similarly, Gly-Sar-induced jejunal I(sc) response in vitro was abolished. The dipeptide-induced increase in fluid absorption in vivo was also abolished in animals lacking PEPT1. Since PEPT1 acts as an acid loader in enterocytes, enterocyte pH(i) was measured in vivo by two-photon microscopy in SNARF-4-loaded villous enterocytes of exteriorized jejuni in anesthetized mice, as well as in BCECF-loaded enterocytes of microdissected jejunal villi. Gly-Sar-induced pH(i) decrease was no longer observed in the absence of PEPT1. A reversal of the proton gradient across the luminal membrane did not significantly diminish Gly-Sar-induced I(sc) response, whereas a depolarization of the apical membrane potential by high K(+) or via Na(+)-K(+)-ATPase inhibition strongly diminished Gly-Sar-induced I(sc) responses. This study demonstrates for the first time that proton-coupled electrogenic dipeptide uptake in the native small intestine, mediated by PEPT1, relies on the negative apical membrane potential as the major driving force and contributes significantly to intestinal fluid transport.
AJP Gastrointestinal and Liver Physiology 07/2010; 299(1):G265-74. · 3.43 Impact Factor
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HUI CHANG,
MANTIAN MI,
WENHUA LING,
JUNDONG ZHU,
QIANYONG ZHANG,
NA WEI,
YONG ZHOU,
YONG TANG,
XIAOPING YU,
TIN ZHANG, JIAN WANG,
JIALIN YUAN
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ABSTRACT: The cytotoxicity and apoptosis induction effect of 23 flavonoids on human leukemia cells (HL-60) were investigated. 3,6-Dihydroxyflavone, luteolin and geraldol showed the most potent cytotoxic effect. By comparing the cytotoxicity of selected molecules that differ in only one structure element, we identified several structural properties important for potent cytotoxic activity, including the presence of 2,3-double bond, appropriate hydroxyl numbers, 3-OH and ortho-OH in ring B. Flavonoids with a 5-OH exhibited lower cytotoxicity than their counterparts. The intracellular reactive oxygen species (ROS) detection showed that 3,6-dihydroxyflavone, luteolin and geraldol all caused ROS generation. Addition of antioxidant N-acetylcysteine prevented the elevation of ROS induced by the three flavonoids and partially suppressed their cytotoxic effects. It implied that pro-oxidation was involved in the apoptotic response, and ROS generation plays an important role in the antitumor effect of flavonoids.PRACTICAL APPLICATIONSFlavonoids exist extensively in foods and herbal products, and several beneficial biological activities have been demonstrated. Development of compounds with anticancer and other pharmacological effects from natural products has currently become a very important topic. Our study revealed structurally related anticancer activities of 23 flavonoids on HL-60 cells and indicated that 3,6-dihydroxyflavone, luteolin and geraldol were active anticancer compounds via pro-oxidation and apoptosis induction. These findings should be useful for developing potent anticancer compounds from flavonoids for potential clinical application.
Journal of Food Biochemistry 03/2010; 34(s1):1 - 14. · 0.81 Impact Factor
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ABSTRACT: Carbonic anhydrase (CA) is strongly expressed in the duodenum and has been implicated in a variety of physiological functions including enterocyte HCO(3)(-) supply for secretion and the "sensing" of luminal acid and CO(2). Here, we report the physiological role of the intracellular CAII isoform involvement in acid-, PGE(2,) and forskolin-induced murine duodenal bicarbonate secretion (DBS) in vivo. CAII-deficient and WT littermates were studied in vivo during isoflurane anesthesia. An approximate 10-mm segment of the proximal duodenum with intact blood supply was perfused under different experimental conditions and DBS was titrated by pH immediately. Two-photon confocal microscopy using the pH-sensitive dye SNARF-1F was used to assess duodenocyte pH(i) in vivo. After correction of systemic acidosis by infusion of isotonic Na(2)CO(3), basal DBS was not significantly different in CAII-deficient mice and WT littermates. The duodenal bicarbonate secretory response to acid was almost abolished in CAII-deficient mice, but normal to forskolin- or 16,16-dimethyl PGE(2) stimulation. The complete inhibition of tissue CAs by luminal methazolamide and i.v. acetazolamide completely blocked the response to acid, but did not significantly alter the response to forskolin. While duodenocytes acidified upon luminal perfusion with acid, no significant pH(i) change occurred in CAII-deficient duodenum in vivo. The results suggest that CA II is important for duodenocyte acidification by low luminal pH and for eliciting the acid-mediated HCO(3)(-) secretory response, but is not important in the generation of the secreted HCO(3)(-) ions.
Proceedings of the National Academy of Sciences 08/2009; 106(31):13094-9. · 9.68 Impact Factor
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Chinese Journal of Chemistry 12/2008; 26(12):2261 - 2266. · 0.75 Impact Factor
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ABSTRACT: Knockout mouse models have provided key insights into the physiological significance of many intestinal electrolyte transporters. This review has selected three examples to highlight the importance of knockout mouse technology in unravelling complex regulatory relationships important for the understanding of human diseases. Genetic ablation of the cystic fibrosis transmembrane conductance regulator (CFTR) has created one of the most useful mouse models for understanding intestinal transport. Recent work has provided an understanding of the key role of the CFTR anion channel in the regulation of HCO3− secretion, and the important consequences that a defect in HCO3− output may have on the viscoelastic properties of mucus, on lipid absorption and on male and female reproductive function. The regulation of CFTR activity, and also that of the intestinal salt absorptive transporter NHE3, occurs via the formation of PSD95-Drosophila homologue Discs-large-tight junction protein ZO-1 (PDZ) adaptor protein-mediated multiprotein complexes. The recent generation of knockout mice for three members of the sodium-hydrogen regulatory factor (NHERF) family of PDZ adaptor proteins, namely NHERF1 (EBP50), NHERF2 (E3KARP) and NHERF3 (PDZK1), has helped to explain why NHERF1 is essential for both normal and mutant CFTR function. In addition, they have provided new insight into the molecular mechanisms of secretory diarrhoeas. Genetic ablation of members of the recently discovered Slc26 anion transporter gene family not only reproduced the phenotype of the genetic diseases that led to the discovery of the gene family, but also resulted in new insights into complex human diseases such as secretory diarrhoea, fructose-induced hypertension and urolithiasis.
Experimental physiology 11/2008; 94(2):175 - 179. · 3.17 Impact Factor
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Journal of Polymer Science Part A Polymer Chemistry 10/2008; 46(23):7690 - 7701. · 3.92 Impact Factor
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Advanced Synthesis & Catalysis 05/2007; 349(7):1052 - 1056. · 6.05 Impact Factor
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ABSTRACT: The objective of this study was to determine if hedonically different sweetness levels in yogurt, determined by the ideal-relative rating methods, affected the consumption of yogurt in a sensory specific satiety test. Fifteen subjects attended a preliminary session, six taste tests and three sensory specific satiety tests. During each taste test, subjects rated yogurt with one of the three levels of sweetness (high, optimum, and low) for six attributes. During each sensory specific satiety test, subjects were offered a large serving of yogurt with one of the sweetness levels. Liking for optimum or high sweet yogurts decreased more after consumption than the liking for the low sweet yogurt, however, the consumption of optimum and high sweet yogurts was also greater, thus confounding the experiment.
Journal of Sensory Studies 05/2007; 13(4):377 - 388. · 1.60 Impact Factor
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Journal of Computational Chemistry 01/2007; 28(5):865 - 876. · 4.58 Impact Factor
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Advanced Synthesis & Catalysis 11/2006; 348(16‐17):2385 - 2390. · 6.05 Impact Factor
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ABSTRACT: Additive, dominance genetic effects were analysed for body weight (BW) and seven morphometric traits from three variants of red common carp, Cyprinus carpio var. singuonensis, C. carpio var. wuyuanensis and C. carpio var. color, based on a diallel cross-mating design by using the additive–dominance genetic model. The results indicated that at 8 months of age (juvenile stage), the traits of pre-dorsal height (PDH), pre-dorsal width (PDW) and caudal peduncle height (CPH) were mainly controlled by additive effects; the traits of BW, total length (TL), standard length (SL), head length (HL) and caudal peduncle length (CPL) were mainly controlled by dominance effects. The narrow-sense heritabilities of all traits ranged from 0.000 to 0.556; however, the broad-sense heritabilities ranged from 0.453 to 0.775. At 20 months of age (adult stage), the traits of TL, SL, PDH and CPL were mainly controlled by additive effects, whereas the traits of BW, PDW, HL and CPH were mainly controlled by dominance effects. The narrow-sense heritabilities of all traits ranged from 0.000 to 0.710; the broad-sense heritabilities ranged from 0.629 to 0.934. Through the genetic merit prediction from three parents, it was found that the additive and dominance effects of C. carpio var. color could increase the BW and body length in their progeny, but these two genetic effects of C. carpio var. singuonensis and C. carpio var. wuyuanensis could decrease BW in their progeny. The genetic effects of C. carpio var. wuyuanensis could reduce total length, SL and caudal peduncle length, but increase body height in their progeny.
Aquaculture Research 09/2006; 37(14):1481 - 1486. · 1.20 Impact Factor
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ABSTRACT: The polymerizations of styrene (St), methyl acrylate (MA), and butyl acrylate (BuA), carried out under UV irradiation at room temperature in the presence of dibenzyl trithiocarbonate (DBTTC) were found to display living free-radical polymerization characteristics as evidenced by: narrow molecular weight distribution, linear increase of molecular weight with increasing conversion, well-controlled molecular weight, and first-order polymerization kinetics. The triblock copolymer, PMA-PSt-PMA, with narrow polydispersity and well-defined structure was successfully prepared using PMA-S-C(=S)-S-PMA as macro-photoinitiator under UV irradiation at room temperature. Based on GPC, NMR and FT-IR analyses, the structures of the polymers were obtained and the mechanism of the polymerization was proposed.
Macromolecular Chemistry and Physics 02/2002; 203(3):477 - 483. · 2.36 Impact Factor
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ABSTRACT: The controlled free radical polymerization of (2,2-dimethyl-1,3-dioxolan-4-yl)methyl acrylate (DMDMA) was achieved by atom transfer radical polymerization (ATRP) in tetrahydrofuran (THF, 50%, v/v) solution at 90°C with the discotic six-functional initiator, 2,3,6,7,10,11-hexakis(2-bromobutyryloxy) triphenylene (HBTP). The 6-armed polyDMDMA with low polydispersity index (M̄w/M̄n = 1.52–1.32) was obtained. The copolymerization of DMDMA with styrene (St) using 6-armed polySt-Br as macroinitiator was carried out, and the GPC traces of the copolymers obtained were unimodal and symmetrical, indicating complete conversion of the macroinitiator into block copolymer. The star-shaped block copolymers with different segment compositions and narrower polydispersity (1.21–1.24) were synthesized, and subsequent hydrolysis of the acetal-protecting group in 1 N HCl THF solution produced poly[St-b-(2,3-dihydroxypropyl)acrylate] [poly(St-b-DHPA)], which was verified by IR and NMR spectroscopy.
Macromolecular Chemistry and Physics 12/2001; 202(17):3403 - 3409. · 2.36 Impact Factor
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Journal of Polymer Science Part A Polymer Chemistry 05/2001; 39(13):2134 - 2142. · 3.92 Impact Factor
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ABSTRACT: Molybdenum-catalyzed asymmetric allylic alkylation reactions were carried out using the inexpensive, air-stable, and readily available Mo(CO)6 as precatalyst. In situ IR was used to determine the required activation time and temperature required to achieve the maximum concentration of the ‘‘active’’ catalyst from the molybdenum-precatalyst and chiral ligand. Results from comparison studies are consistent with the notion that the same active catalyst is generated regardless of molybdenum-precatalyst.
Advanced Synthesis & Catalysis 02/2001; 343(1):46 - 50. · 6.05 Impact Factor
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