scholarly journals Argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis

2014 ◽  
Vol 307 (3) ◽  
pp. G347-G354 ◽  
Author(s):  
M. H. Premkumar ◽  
G. Sule ◽  
S. C. Nagamani ◽  
S. Chakkalakal ◽  
A. Nordin ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Protective Role ◽  
Intestinal Epithelial ◽  
Argininosuccinate Lyase ◽  
Mortality And Morbidity ◽  
Novel Approach ◽  
Enterocyte Apoptosis ◽  
Epithelial Cell Lines ◽  
A Cell ◽  
Gastrointestinal Emergency

Necrotizing enterocolitis (NEC), the most common neonatal gastrointestinal emergency, results in significant mortality and morbidity, yet its pathogenesis remains unclear. Argininosuccinate lyase (ASL) is the only enzyme in mammals that is capable of synthesizing arginine. Arginine has several homeostatic roles in the gut and its deficiency has been associated with NEC. Because enterocytes are the primary sites of arginine synthesis in neonatal mammals, we evaluated the consequences of disruption of arginine synthesis in the enterocytes on the pathogenesis of NEC. We devised a novel approach to study the role of enterocyte-derived ASL in NEC by generating and characterizing a mouse model with enterocyte-specific deletion of Asl ( Asl flox/flox; VillinCre tg/+, or CKO). We hypothesized that the presence of ASL in a cell-specific manner in the enterocytes is protective in the pathogenesis of NEC. Loss of ASL in enterocytes resulted in an increased incidence of NEC that was associated with a proinflammatory state and increased enterocyte apoptosis. Knockdown of ASL in intestinal epithelial cell lines resulted in decreased migration in response to lipopolysaccharide. Our results show that enterocyte-derived ASL has a protective role in NEC.

Necrotizing Enterocolitis Mortality: A New Parameter to Predict High Risk

2021 ◽  
Vol 35 (1) ◽  
pp. 10-19
Author(s):  
Miriam García ◽  
Isabel Casal ◽  
Sonia Pértega ◽  
Cristina González ◽  
Jesús Caramés Bouzán
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Necrotizing Enterocolitis ◽  
Serum Proteins ◽  
Analytical Data ◽  
Ethical Review ◽  
Mortality And Morbidity ◽  
Patient Demographics ◽  
Low Levels ◽  
Gastrointestinal Emergency

Introduction: Necrotizing enterocolitis, is the most common gastrointestinal emergency in the preterm infant and is associated with high mortality and morbidity. Predict which infants will progress to more severity stages of the illness and are in high risk for mortality is one of the challenges in relation to this disease. The objective of this study is to identify which factors are associated with mortality in infants diagnoses of NEC in our centre along a 12-year period. Material and Methods: A total of 124 consecutively patients were included in the study diagnosed of NEC at the Complejo Hospitalario Universitario de A Coruña, Spain. Information was obtained from medical records to compare patient demographics characteristics, prenatal information, clinical and radiological findings, relevant analytical data, therapeutic management and outcomes of infants who survived NEC and infants who died. Informed consent and ethical review board was obtained. Associations were analyzed by bivariate and multivariate analysis. Results: Among 124 patients, 110 patients survived NEC and 14 died. In multivariate analysis, the patients who died presented at birth low Apgar levels at minute one, apneas in the neonatal period, coagulopathy and low levels of serum proteins at diagnoses of NEC.

scholarly journals Lactobacillus bulgaricus Prevents Intestinal Epithelial Cell Injury Caused by Enterobacter sakazakii-Induced Nitric Oxide both In Vitro and in the Newborn Rat Model of Necrotizing Enterocolitis

2008 ◽  
Vol 77 (3) ◽  
pp. 1031-1043 ◽  
Author(s):  
Catherine J. Hunter ◽  
Monica Williams ◽  
Mikael Petrosyan ◽  
Yigit Guner ◽  
Rahul Mittal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Necrotizing Enterocolitis ◽  
Rat Model ◽  
Lactobacillus Bulgaricus ◽  
No Production ◽  
Intestinal Epithelial ◽  
Enterobacter Sakazakii ◽  
Newborn Rat ◽  
Enterocyte Apoptosis

ABSTRACT Enterobacter sakazakii is an emerging pathogen that has been associated with outbreaks of necrotizing enterocolitis (NEC) as well as infant sepsis and meningitis. Our previous studies demonstrated that E. sakazakii induces NEC in a newborn rat model by inducing enterocyte apoptosis. However, the mechanisms responsible for enterocyte apoptosis are not known. Here we demonstrate that E. sakazakii induces significant production of nitric oxide (NO) in rat intestinal epithelial cells (IEC-6) upon infection. The elevated production of NO, which is due to increased expression of inducible NO synthase, is responsible for apoptosis of IEC-6 cells. Notably, pretreatment of IEC-6 cells with Lactobacillus bulgaricus (ATCC 12278) attenuated the upregulation of NO production and thereby protected the cells from E. sakazakii-induced apoptosis. Furthermore, pretreatment with L. bulgaricus promoted the integrity of enterocytes both in vitro and in the infant rat model of NEC, even after challenge with E. sakazakii. Infection of IEC-6 cells with E. sakazakii upregulated several genes related to apoptosis, cytokine production, and various signaling pathways, as demonstrated by rat gene array analysis, and this upregulation was subdued by pretreatment with L. bulgaricus. In agreement with these data, L. bulgaricus pretreatment protected newborn rats infected with E. sakazakii from developing NEC, resulting in improved survival.

Development of a Cell-Based Assay for Identifying KCa3.1 Inhibitors Using Intestinal Epithelial Cell Lines

2020 ◽  
pp. 247255522095066
Author(s):  
Chanon Jakakul ◽  
Phongthon Kanjanasirirat ◽  
Chatchai Muanprasat
Keyword(s):  
Epithelial Cell ◽  
High Throughput Screening ◽  
Intestinal Epithelial Cell ◽  
Therapeutic Potential ◽  
Intestinal Epithelial ◽  
T84 Cells ◽  
Screening Assay ◽  
Epithelial Cell Lines ◽  
A Cell ◽  
Screening Platform

Inhibition of the KCa3.1 potassium channel has therapeutic potential in a variety of human diseases, including inflammation-associated disorders and cancers. However, KCa3.1 inhibitors with high therapeutic promise are currently not available. This study aimed to establish a screening assay for identifying inhibitors of KCa3.1 in native cells and from library compounds derived from natural products in Thailand. The screening platform was successfully developed based on a thallium flux assay in intestinal epithelial (T84) cells with a Z′ factor of 0.52. The screening of 1352 compounds and functional validation using electrophysiological analyses identified 8 compounds as novel KCa3.1 inhibitors with IC50 values ranging from 0.14 to 6.57 µM. These results indicate that the assay developed is of excellent quality for high-throughput screening and capable of identifying KCa3.1 inhibitors. This assay may be useful in identifying novel KCa3.1 inhibitors that may have therapeutic potential for inflammation-associated disorders and cancers.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

scholarly journals The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phage ZCSE2 as a Novel Approach to Combat Multidrug-Resistant Salmonella enterica

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 678
Author(s):  
Abdallah S. Abdelsattar ◽  
Rana Nofal ◽  
Salsabil Makky ◽  
Anan Safwat ◽  
Amera Taha ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Color Change ◽  
Antibacterial Properties ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Mortality And Morbidity ◽  
Novel Approach ◽  
Transmission Electron

The emergence and evolution of antibiotic-resistant bacteria is considered a public health concern. Salmonella is one of the most common pathogens that cause high mortality and morbidity rates in humans, animals, and poultry annually. In this work, we developed a combination of silver nanoparticles (AgNPs) with bacteriophage (phage) as an antimicrobial agent to control microbial growth. The synthesized AgNPs with propolis were characterized by testing their color change from transparent to deep brown by transmission electron microscopy (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). The phage ZCSE2 was found to be stable when combined with AgNPs. Both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated for AgNPs, phage, and their combination. The results indicated that MIC and MBC values were equal to 23 µg/mL against Salmonella bacteria at a concentration of 107 CFU/mL. The combination of 0.4× MIC from AgNPs and phage with Multiplicity of Infection (MOI) 0.1 showed an inhibitory effect. This combination of AgNPs and phage offers a prospect of nanoparticles with significantly enhanced antibacterial properties and therapeutic performance.

scholarly journals The Protective Role of Dormant Origins in Response to Replicative Stress

2018 ◽  
Vol 19 (11) ◽  
pp. 3569 ◽  
Author(s):  
Lilas Courtot ◽  
Jean-Sébastien Hoffmann ◽  
Valérie Bergoglio
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Replication Timing ◽  
Protective Role ◽  
Entire Genome ◽  
Replicative Stress ◽  
A Cell ◽  
The Many

Genome stability requires tight regulation of DNA replication to ensure that the entire genome of the cell is duplicated once and only once per cell cycle. In mammalian cells, origin activation is controlled in space and time by a cell-specific and robust program called replication timing. About 100,000 potential replication origins form on the chromatin in the gap 1 (G1) phase but only 20–30% of them are active during the DNA replication of a given cell in the synthesis (S) phase. When the progress of replication forks is slowed by exogenous or endogenous impediments, the cell must activate some of the inactive or “dormant” origins to complete replication on time. Thus, the many origins that may be activated are probably key to protect the genome against replication stress. This review aims to discuss the role of these dormant origins as safeguards of the human genome during replicative stress.

Asymmetrical targeting of type II Na-Picotransporters in renal and intestinal epithelial cell lines

2000 ◽  
Vol 278 (3) ◽  
pp. F361-F368 ◽  
Author(s):  
N. Hernando ◽  
S. Sheikh ◽  
Z. Karim-Jimenez ◽  
H. Galliker ◽  
J. Forgo ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Fluorescent Protein ◽  
Intestinal Epithelial ◽  
Type Ii ◽  
Opossum Kidney ◽  
Epithelial Cell Lines ◽  
Molecular Determinants ◽  
Cellular Context ◽  
Green Fluorescent

Targeting of newly synthesized transporters to either the apical or basolateral domains of polarized cells is crucial for the function of epithelia, such as in the renal proximal tubule or in the small intestine. Recently, different sodium-phosphate cotransporters have been identified. Type II cotransporters can be subdivided into two groups: type IIa and type IIb. Type IIa is predominantly expressed in renal proximal tubules, whereas type IIb is located on the intestinal and lung epithelia. To gain some insights into the polarized targeting of the type II cotransporters, we have transiently expressed type IIa and type IIb cotransporters in several epithelial cell lines: two lines derived from renal proximal cells (opossum kidney and LLC-PK1), one from renal distal cells (Madin-Darby canine kidney), and one from colonic epithelium (CaCo-2). We studied the expression of the transporters fused to the enhanced green fluorescent protein. Our data indicate that the polarized targeting is dependent on molecular determinants most probably located at the COOH terminus of the cotransporters as well as on the cellular context.

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