ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2008
Platelet-activating factor-induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Development of a predictive model for severe adverse outcomes following surgery for neonatal necrotizing enterocolitis: a nomogram study based on postoperative intestinal failure beyond 42 days and death.Frontiers in pediatrics · 2025Article
- Chloride/proton antiporters ClC3 and ClC5 support bone formation in mice.Bone reports · 2024Article
- Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.Cellular and molecular life sciences : CMLS · 2021Review
- 5‑Nitro‑2‑(3‑phenylpropylamino) benzoic acid induces apoptosis of human lens epithelial cells via reactive oxygen species and endoplasmic reticulum stress through the mitochondrial apoptosis pathway.International journal of molecular medicine · 2021Article
- Threonine532 phosphorylation in ClC-3 channels is required for angiotensin II-induced Cl(-) current and migration in cultured vascular smooth muscle cells.British journal of pharmacology · 2016Article
- Chloride-hydrogen antiporters ClC-3 and ClC-5 drive osteoblast mineralization and regulate fine-structure bone patterning in vitro.Physiological reports · 2015Article
- Platelet-activating factor: a role in preterm delivery and an essential interaction with Toll-like receptor signaling in mice.Biology of reproduction · 2014Article
- Platelet-activating factor contributes to Bacillus anthracis lethal toxin-associated damage.The Journal of biological chemistry · 2014Article
- Deficiency of phospholipase A2 group 7 decreases intestinal polyposis and colon tumorigenesis in Apc(Min/+) mice.Cancer research · 2013Article
- Lactobacillus acidophilus alleviates platelet-activating factor-induced inflammatory responses in human intestinal epithelial cells.PloS one · 2013Article
- Recent advances in small bowel diseases: Part I.World journal of gastroenterology · 2012Review
- Defining signal transduction by inositol phosphates.Sub-cellular biochemistry · 2012Review
- Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent.Inflammatory bowel diseases · 2010Article
- Neonatal Necrotizing Enterocolitis -Inflammation and Intestinal Immaturity.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2009Article
- Molecular basis for the integration of inositol phosphate signaling pathways via human ITPK1.Advances in enzyme regulation · 2009Review
- An expanded biological repertoire for Ins(3,4,5,6)P4 through its modulation of ClC-3 function.Current biology : CB · 2008Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Platelet-activating factor (PAF) is a phospholipid inter- and intracellular mediator implicated in intestinal injury primarily via induction of an inflammatory cascade. We find that PAF also has direct pathological effects on intestinal epithelial cells (IEC). PAF induces Cl(-) channel activation, which is associated with intracellular acidosis and apoptosis. Using the rat small IEC line IEC-6, electrophysiological experiments demonstrated that PAF induces Cl(-) channel activation. This PAF-activated Cl(-) current was inhibited by Ca(2+) chelation and a calcium calmodulin kinase II inhibitor, suggesting PAF activation of a Ca(2+)-activated Cl(-) channel. To determine the pathological consequences of Cl(-) channel activation, microfluorimetry experiments were performed, which revealed PAF-induced intracellular acidosis, which is also inhibited by the Cl(-) channel inhibitor 4,4'diisothiocyanostilbene-2,2'disulfonic acid and Ca(2+) chelation. PAF-induced intracellular acidosis is associated with caspase 3 activation and DNA fragmentation. PAF-induced caspase activation was abolished in cells transfected with a pH compensatory Na/H exchanger construct to enhance H(+) extruding ability and prevent intracellular acidosis. As ClC-3 is a known intestinal Cl(-) channel dependent on both Ca(2+) and calcium calmodulin kinase II phosphorylation, we generated ClC-3 knockdown cells using short hairpin RNA. PAF induced Cl(-) current; acidosis and apoptosis were all significantly decreased in ClC-3 knockdown cells. Our data suggest a novel mechanism of PAF-induced injury by which PAF induces intracellular acidosis via activation of the Ca(2+)-dependent Cl(-) channel ClC-3, resulting in apoptosis of IEC.
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