ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2008
Polyunsaturated fatty acids block platelet-activating factor-induced phosphatidylinositol 3 kinase/Akt-mediated apoptosis in 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 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Physiological Significance and Functions of AA.Reviews of physiology, biochemistry and pharmacology · 2027Review
- Role of Platelet-activating factor and HO-1 in mediating the protective effect of rupatadine against 5-fluorouracil-induced hepatotoxicity in rats.Environmental science and pollution research international · 2022Article
- The Role of Dietary Fats in the Development and Prevention of Necrotizing Enterocolitis.Nutrients · 2021Review
- Boosting Akt Pathway by Rupatadine Modulates Th17/Tregs Balance for Attenuation of Isoproterenol-Induced Heart Failure in Rats.Frontiers in pharmacology · 2021Article
- Necrotizing enterocolitis: It's not all in the gut.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Comparing the role of Ginkgolide B and Ginkgolide K on cultured astrocytes exposed to oxygen‑glucose deprivation.Molecular medicine reports · 2018Article
- Pathogenesis of NEC: Role of the innate and adaptive immune response.Seminars in perinatology · 2017Review
- Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid.The Journal of biological chemistry · 2016Article
- Inflammatory signaling in NEC: Role of NF-κB, cytokines and other inflammatory mediators.Pathophysiology : the official journal of the International Society for Pathophysiology · 2014Article
- Update in pathogenesis and prospective in treatment of necrotizing enterocolitis.BioMed research international · 2014Review
- Platelet-activating factor induces proliferation in differentiated keratinocytes.Molecular and cellular biochemistry · 2013Article
- Deficiency of phospholipase A2 group 7 decreases intestinal polyposis and colon tumorigenesis in Apc(Min/+) mice.Cancer research · 2013Article
- Inflammatory signaling in necrotizing enterocolitis.Clinics in perinatology · 2013Review
- Lactobacillus acidophilus alleviates platelet-activating factor-induced inflammatory responses in human intestinal epithelial cells.PloS one · 2013Article
- Innate immune signaling in the pathogenesis of necrotizing enterocolitis.Clinical & developmental immunology · 2013Review
- Recent advances in small bowel diseases: Part I.World journal of gastroenterology · 2012Review
- Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice.Journal of pediatric gastroenterology and nutrition · 2012Article
- Palmitoylated TMX and calnexin target to the mitochondria-associated membrane.The EMBO journal · 2012Article
- Necrotizing enterocolitis.The New England journal of medicine · 2011Review
- Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent.Inflammatory bowel diseases · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have shown earlier that platelet-activating factor (PAF) causes apoptosis in enterocytes via a mechanism that involves Bax translocation to mitochondria, followed by caspase activation and DNA fragmentation. Herein we report that, in rat small intestinal epithelial cells (IEC-6), these downstream apoptotic effects are mediated by a PAF-induced inhibition of the phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (Akt) signaling pathway. Treatment with PAF results in rapid dephosphorylation of Akt, phosphoinositide-dependent kinase-1, and the YXXM p85 binding motif of several proteins and redistribution of Akt-pleckstrin homology domain-green fluorescent protein, i.e., an in vivo phosphatidylinositol (3,4,5)-trisphosphate sensor, from membrane to cytosol. The proapoptotic effects of PAF were inhibited by both n-3 and n-6 polyunsaturated fatty acids but not by a saturated fatty acid palmitate. Indomethacin, an inhibitor of prostaglandin biosynthesis, did not influence the baseline or PAF-induced apoptosis, but 2-bromopalmitate, an inhibitor of protein palmitoylation, inhibited all of the proapoptotic effects of PAF. Our data strongly suggest that an inhibition of the PI 3-kinase/Akt signaling pathway is the main mechanism of PAF-induced apoptosis in enterocytes and that polyunsaturated fatty acids block this mechanism very early in the signaling cascade independently of any effect on prostaglandin synthesis, and probably directly via an effect on protein palmitoylation.
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