Abstract:Objective-Barrett's oesophagus is a premalignant disease associated with oesophageal adenocarcinoma. The major goal of this study was to determine the mechanism responsible for bile acid-induced alteration in intracellular pH (pH i ) and its effect on DNA damage in cells derived from normal oesophagus (HET1A) or Barrett's oesophagus (CP-A).Design-Cells were exposed to bile acid cocktail (BA) and/or acid in the presence/absence of inhibitors of nitric oxide synthase (NOS) or sodium-hydrogen exchanger (NHE). Nit… Show more
“…Indeed, acid-mediated cellular injury induced Dkk1 overexpression in vitro. This effect was directly linked to acid-mediated DNA damage (14), just as the esophageal epithelial cells respond to alternative inducers of DNA injury such as camptothecin by upregulating Dkk1. In favor of this observation, Dkk1 transcriptional activation has been associated with the p53 tumor suppressor, the activation of which has been reported upon cellular stress accompanied by DNA damage (30,50,52).…”
Section: Discussionmentioning
confidence: 99%
“…In response to injury, cells will undergo senescence, or they will self-destruct (apoptosis), if the damage cannot be easily repaired. In GERD, squamous epithelial cells are continuously injured by the gastric refluxate, which induces oxidative stress and DNA damage (14,24). As the GERD injury persists, more surface epithelial cells are damaged, and the injury progresses to the deeper layers of the epithelium.…”
Section: Discussionmentioning
confidence: 99%
“…Characteristically, brain tumor cells respond to DNA damage by elevating Dkk1 expression (44), while activation of IFN-␥ and TNF-␣ signaling pathways has been reported upstream of Dkk1 overexpression in colitis and rheumatoid arthritis (26,49). In reflux esophagitis, the cellular injury is triggered by intraluminal stressors, such as acid and bile, and results in DNA damage (14) and activation of multifaceted inflammatory mechanisms (42). In this study, we emphasized the effect of acid, based on the high Dkk1 levels reported in the normallooking mucosa of esophagitis patients, away from the margins of the reflux-induced lesions/erosions, suggesting that Dkk1 is more likely affected by intraluminal stressors than by inflammatory mediators (2).…”
Lyros O, Rafiee P, Nie L, Medda R, Jovanovic N, Schmidt J, Mackinnon A, Venu N, Shaker R. Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.
“…Indeed, acid-mediated cellular injury induced Dkk1 overexpression in vitro. This effect was directly linked to acid-mediated DNA damage (14), just as the esophageal epithelial cells respond to alternative inducers of DNA injury such as camptothecin by upregulating Dkk1. In favor of this observation, Dkk1 transcriptional activation has been associated with the p53 tumor suppressor, the activation of which has been reported upon cellular stress accompanied by DNA damage (30,50,52).…”
Section: Discussionmentioning
confidence: 99%
“…In response to injury, cells will undergo senescence, or they will self-destruct (apoptosis), if the damage cannot be easily repaired. In GERD, squamous epithelial cells are continuously injured by the gastric refluxate, which induces oxidative stress and DNA damage (14,24). As the GERD injury persists, more surface epithelial cells are damaged, and the injury progresses to the deeper layers of the epithelium.…”
Section: Discussionmentioning
confidence: 99%
“…Characteristically, brain tumor cells respond to DNA damage by elevating Dkk1 expression (44), while activation of IFN-␥ and TNF-␣ signaling pathways has been reported upstream of Dkk1 overexpression in colitis and rheumatoid arthritis (26,49). In reflux esophagitis, the cellular injury is triggered by intraluminal stressors, such as acid and bile, and results in DNA damage (14) and activation of multifaceted inflammatory mechanisms (42). In this study, we emphasized the effect of acid, based on the high Dkk1 levels reported in the normallooking mucosa of esophagitis patients, away from the margins of the reflux-induced lesions/erosions, suggesting that Dkk1 is more likely affected by intraluminal stressors than by inflammatory mediators (2).…”
Lyros O, Rafiee P, Nie L, Medda R, Jovanovic N, Schmidt J, Mackinnon A, Venu N, Shaker R. Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.
“…GERD and Barrett's esophagus are identified as major risk factors for esophageal carcinoma. Besides acid reflux, bile reflux can be a clinical challenge due to refractory GERD and it may also play an important role in the progression from Barrett's to adenocarcinoma [5,6] . It is worth drawing attention to studies performed on animal models by Konturek et al [7] .…”
Symptomatic gastro-esophageal reflux disease (GERD) is a very common disease. The consequence of GERD is not only erosive esophagitis, but also esophageal stricture, Barrett's esophagus and extra-esophageal damage (including the lungs, throat, sinuses, middle ear and teeth). GERD and Barrett's esophagus are also identified as major risk factors for esophageal carcinoma. Therapy with melatonin prevents esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals, then further studies are required in humans to establish whether a melatonin supplement is able to protect the patients with GERD from erosions, Barrett's and neoplasia.
“…Several studies have shown that bile acids induce intracellular acidification in various cell types [68,[95][96][97]. At first step, we have investigated the effect of CDCA and UDCA on basal pH i of pancreatic ducts.…”
Section: Effect Of Udca and Cdca On Ph Imentioning
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.