Platelet-Activating Factor Regulates Chloride Transport in Colonic Epithelial Cell Monolayers

Claud, Erika C.

doi:10.1203/01.pdr.0000023173.89966.19

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…Interestingly, PAF protects lymphocytes from apoptosis (46), whereas it is a potent proapoptotic molecule in a variety of cell types such as hippocampus-derived cells (43), human epidermal cells (3), astrocytes, and oligodendrocytes (24). Intestinal epithelial cells (IECs) express PAF receptor (34), and we have shown that PAF receptor is present exclusively in the apical plasma membrane and its activation leads to regulation of transepithelial ion transport in colonocytes (15). Curiously, PAF activates epithelial functions at a much higher concentration than in other cell types (15,45).…”

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confidence: 95%

“…Intestinal epithelial cells (IECs) express PAF receptor (34), and we have shown that PAF receptor is present exclusively in the apical plasma membrane and its activation leads to regulation of transepithelial ion transport in colonocytes (15). Curiously, PAF activates epithelial functions at a much higher concentration than in other cell types (15,45). We hypothesized that PAF induces apoptosis in enterocytes and that a combined antiapoptotic effect on lymphocytes and a proapoptotic effect on enterocytes may be a plausible explanation for the potent injurious nature of PAF in the intestine.…”

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Platelet-activating factor-induced apoptosis is blocked by Bcl-2 in rat intestinal epithelial cells

Lü¹,

Caplan²,

Saraf³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Plateletactivating factor (PAF) is a key mediator in pathogenesis of inflammatory bowel diseases (IBDs) but mechanisms of PAF-induced mucosal injury are poorly understood. To determine whether apoptosis and the Bcl-2-family of apoptosis regulatory gene products play a role in PAF-induced mucosal injury, we stably and conditionally overexpressed bcl-2 in rat small intestinal epithelial cells-6 under the control of a lactose-inducible promoter. Western blot analysis and immuno-histochemistry were used to verify inducible Bcl-2 and to analyze Bcl-2 and a proapoptotic member of the Bcl-2 family, Bax, subcellular distribution. DNA fragmentation was quantified by ELISA, caspase activity was measured by using fluorogenic peptide substrates, and mitochondrial membrane potential was assayed by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and fluorescence digital imaging. Bcl-2 expression was highly inducible by lactose analog isopropyl-beta-(d)-thiogalactoside (IPTG) and was localized predominantly to mitochondria. In the absence of bcl-2 overexpression and after treatment with PAF, Bax translocated to mitochondria, and mitochondrial membrane potential collapsed within 1 h, followed by caspase-3 activation, which peaked at 6 h with an ensuing DNA fragmentation maximizing at 18 h. After IPTG-induction of bcl-2 expression, PAF failed to induce DNA fragmentation, caspase-3 activation, Bax translocation, or a collapse of mitochondrial membrane potential. These data are the first to show that PAF can activate apoptotic machinery in enterocytes via a mechanism involving Bax translocation and collapse of mitochondrial membrane potential and that both of these events are under control by bcl-2 expression levels. A better understanding of the role of PAF and Bcl-2 family of apoptosis regulators in epithelial cell death might aid design of better therapeutic or preventive strategies for IBDs.

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confidence: 95%

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confidence: 99%

Platelet-activating factor-induced apoptosis is blocked by Bcl-2 in rat intestinal epithelial cells

Lü¹,

Caplan²,

Saraf³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Additional studies have shown that many molecules that decrease NEC may act to decrease apoptosis of intestinal epithelial cells, including EGF, probiotics, HBEGF, and NOD2 [Dvorak et al, 2008;Khailova et al, 2010]. In these studies, PAF stimulates changes in chloride transport that result in intracellular acidification and presumed enzyme dysfunction leading to apoptosis [Claud et al, 2002;. Utilizing Ussing chamber analyses, it was shown that PAF regulates transepithelial ion transport in colonic epithelial cells and that PAFR localizes exclusively to the apical plasma membrane of these cells.…”

Section: Necrotizing Enterocolitismentioning

confidence: 99%

Necrotizing Enterocolitis: Insights into the Pathogenesis of this Challenging Disease

Caplan¹

2013

Colloquium Series on Integrated Systems Physiology: From Molecule to Function

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Platelet-Activating Factor Concentration in the Stool of Human Newborns: Effects of Enteral Feeding and Neonatal Necrotizing Enterocolitis

Amer¹,

Hedlund²,

Rochester³

et al. 2004

Neonatology

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Epidemiologic studies have identified enteral feedings as a risk factor for necrotizing enterocolitis (NEC). Enteral feedings provide the substrate for colonization of the newborn gut with gram-negative bacteria with endotoxin production, which may trigger the production of endogenous inflammatory mediators, including platelet-activating factor (PAF). In this prospective study, we examined the effect of enteral feeding on PAF concentration in the stool of preterm and full-term human newborns. The concentration of PAF levels in stool was measured at the following times: at passage of first meconium, within 24 h prior to the onset of feedings, at the 3rd and 14th day of feeding and at any time confirmed NEC developed. Stool samples also were analyzed for levels of acetylhydrolase, the PAF breakdown enzyme. Stool PAF concentration rose significantly following the start of enteral feedings. The mean PAF concentration for day 14 samples was significantly higher than the mean concentration of meconium samples (4.90 ± 1.03 vs. 1.81 ± 0.38 ng/g, p < 0.05) and day 0 samples (4.90 ± 1.03 vs. 1.79 ± 0.39 ng/g, p < 0.05). For the 7 patients diagnosed with definite NEC, the mean stool PAF concentration was 12.42 ± 0.77 ng/g, significantly elevated compared to the mean PAF levels in stool from healthy infants at all sampling times (p < 0.01). There was no significant change in acetylhydrolase activity at any of the sampling times. Stool PAF concentration increases with the provision of enteral feedings and rises further with the development of NEC. Since stool acetylhydrolase activity remained unchanged, we speculate the increase of PAF in stool likely represents increased PAF production at the local level following the provision of enteral feedings or the development of neonatal necrotizing enterocolitis.

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Platelet-Activating Factor Regulates Chloride Transport in Colonic Epithelial Cell Monolayers

Cited by 3 publications

References 28 publications

Platelet-activating factor-induced apoptosis is blocked by Bcl-2 in rat intestinal epithelial cells

Platelet-activating factor-induced apoptosis is blocked by Bcl-2 in rat intestinal epithelial cells

Necrotizing Enterocolitis: Insights into the Pathogenesis of this Challenging Disease

Platelet-Activating Factor Concentration in the Stool of Human Newborns: Effects of Enteral Feeding and Neonatal Necrotizing Enterocolitis

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