ArticleThe Biochemical journal2008
Role of Fyn and PI3K in H2O2-induced inhibition of apical Cl-/OH- exchange activity in human intestinal epithelial cells.
Article in The Biochemical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Role of SLC4 and SLC26 solute carriers during oxidative stress.Acta physiologica (Oxford, England) · 2022Review
- Fyn Kinase-Mediated PKCδ Y311 Phosphorylation Induces Dopaminergic Degeneration in Cell Culture and Animal Models: Implications for the Identification of a New Pharmacological Target for Parkinson's Disease.Frontiers in pharmacology · 2021Article
- Source of dopamine in gastric juice and luminal dopamine-induced duodenal bicarbonate secretion via apical dopamine DBritish journal of pharmacology · 2020Article
- Identifying new targets for rectal cancer treatment.Oncoscience · 2020Article
- GSTpi regulates VE-cadherin stabilization through promoting S-glutathionylation of Src.Redox biology · 2020Article
- Pathophysiology of IBD associated diarrhea.Tissue barriers · 2018Review
- KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress.Aging cell · 2016Article
- Hydrogen peroxide-induced calcium influx in lung microvascular endothelial cells involves TRPV4.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Mechanisms Underlying Dysregulation of Electrolyte Absorption in Inflammatory Bowel Disease-Associated Diarrhea.Inflammatory bowel diseases · 2015Review
- Oxygen in the regulation of intestinal epithelial transport.The Journal of physiology · 2014Review
- SRC-family tyrosine kinases in oogenesis, oocyte maturation and fertilization: an evolutionary perspective.Advances in experimental medicine and biology · 2014Review
- Molecular transport machinery involved in orchestrating luminal acid-induced duodenal bicarbonate secretion in vivo.The Journal of physiology · 2013Article
- ILK mediates the effects of strain on intestinal epithelial wound closure.American journal of physiology. Cell physiology · 2011Article
- Stimulation of apical Cl⁻/HCO₃⁻(OH⁻) exchanger, SLC26A3 by neuropeptide Y is lipid raft dependent.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Mechanisms underlying modulation of monocarboxylate transporter 1 (MCT1) by somatostatin in human intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2009Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
H(2)O(2) is a highly reactive oxygen metabolite that has been implicated as an important mediator of inflammation-induced intestinal injury associated with ischaemia/reperfusion, radiation and inflammatory bowel disease. Previous studies have shown that H(2)O(2) inhibits NaCl absorption and activates Cl(-) secretion in the rat and rabbit colon. To date, however, almost no information is available with respect to its effect on the human intestinal apical anion exchanger Cl(-)/OH(-) (HCO(3)(-)). The present studies were, therefore, undertaken to examine the direct effects of H(2)O(2) on OH(-) gradient-driven DIDS (4,4'-di-isothiocyanostilbene-2,2'-disulfonate)-sensitive (36)Cl(-) uptake utilizing a post-confluent transformed human intestinal epithelial cell line, Caco-2. Our results demonstrate that H(2)O(2) (1 mM for 60 min) significantly inhibited (approx. 60%; P<0.05) Cl(-)/OH(-) exchange activity in Caco-2 cells. H(2)O(2)-mediated inhibition of Cl(-)/OH(-) exchange activity involved the Src kinase Fyn and PI3K (phosphoinositide 3-kinase)-dependent pathways. H(2)O(2) also induced phosphorylation of Fyn and p85 (the regulatory subunit of PI3K) in Caco-2 cells. Moreover, an increased association of Fyn and p85 was observed in response to H(2)O(2), resulting in the activation of the downstream target PLCgamma1 (phospholipase Cgamma1). Elevated intracellular Ca(2+) levels and PKCalpha (protein kinase Calpha) functioned as downstream effectors of H(2)O(2)-induced PLCgamma1 activation. Our results, for the first time, provide evidence for H(2)O(2)-induced Src kinase Fyn/PI3K complex association. This complex association resulted in the subsequent activation of PLCgamma1 and Ca(2+)-dependent PKCalpha, resulting in the inhibition of Cl(-)/OH(-) exchange activity. These findings suggest that H(2)O(2)-induced inhibition of the Cl(-)/OH(-) exchange process may play an important role in the pathophysiology of diarrhoea associated with inflammatory disorders, where the amount of reactive oxygen species is markedly elevated.
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