TITLE

OESOPHAGEAL CELL LINES SHOW DIFFERENTIAL SUSCEPTIBILITY TO BILE ACID INDUCED APOPTOSIS THAT IS P53 INDEPENDENT

AUTHOR(S)
Darragh, J.; Ross, P.E.; Dillon, J.F.; Kernohan, N.M.; Dettmar, P.W.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA7
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aim: Bile acids are one component of gastric contents that can reflux into the oesophagus in patients with GORD. Bile acids have been shown to induce apoptosis in colonic epithelium and hepatocytes. Similar activity on oesophageal epithelium may contribute to the pathogenesis of GORD. As the effect of bile acids on the oesophagus has not been examined in detail we have investigated the effects of bile acids on apoptosis of established oesophageal cell lines. Methods: Oesophageal cell lines (OE19, OE21, OE33, and KYSE30), a wild type p53 colon cell line (HCT116), and it's derived isogenic p53 null cell line were grown in medium containing different biochemically pure bile acids. Apoptosis was identified by cell morphology, the presence of sub G1 DNA fragments by flow cytometry and detection of activated caspase-3 by Western blot. Results: OE 33 and OE 19 (derived from an adenocarcinoma) exhibited a dose dependent induction of apoptosis in response to deoxycholic acid (DCA) and chenoDCA. The cell lines derived From squamous cancers (OE21 and KYSE30) were resistant to the proapoptotic effect of bile acids. Less hydrophobic bile acids, such as cholic acid and tauroDCA were unable to induce apoptosis. Caspase 3 activation was observed in apoptotic ceils, however p53 protein levels remained unaffected. The proapoptotic activity of DCA was p53 independent, both p53 wild type and null isogenic colonic cell lines being equally sensitive. Conclusion: DCA and chenoDCA induce p53 independent apoptosis in some oesophageal cell lines, although those that exhibit squamous differentiation are resistant. The proapoptotic activity of particular bile acids may contribute to mucosal damage. Our results also suggest that this response may compensate for loss of p53 activity that occurs in oesophageal cancers and that loss of this bile acid induced effect in vivo may favour tumour.
ACCESSION #
9747294

 

Related Articles

  • DYSREGULATION OF MYC NETWORK PROTEINS IN BARRETT'S METAPLASIA. Tselepis, C.; Sharma, N.; Hardy, R. // Gut;Apr2003 Supplement 1, Vol. 52, pA36 

    Barrett's metaplasia is a premalignant lesion predisposing to oesophageal adenocarcinoma. Patients with Barrett's metaplasia have an approximate 0.5-2% annual risk of developing adenocarcinoma, 30-125 times the risk seen in the general population. Barrett's metaplasia is associated with severe...

  • Bile in the Esophagus—Model for a Bile Acid Biosensor. Nehra, Dhiren // Journal of Gastrointestinal Surgery;Feb2010 Supplement 1, Vol. 14, p6 

    Acid and bile acids form important constituents of the refluxed substances in patients who suffer from gastroesophageal reflux disease. Whilst 24h ambulatory pH monitoring using antimony or glass pH electrodes measures acid levels 5 cm above the gastroesophageal junction, there are no reliable...

  • The molecular pathogenesis of Barrett's esophagus: common signaling pathways in embryogenesis metaplasia and neoplasia. Peters, Jeffrey H.; Avisar, N. // Journal of Gastrointestinal Surgery;Feb2010 Supplement 1, Vol. 14, p81 

    Although Barrett's esophagus has been recognized for over 50 years, the cellular and molecular mechanisms leading to the replacement of squamous esophageal epithelium with a columnar type are largely unknown. Barrett's is known to be an acquired process secondary to chronic gastroesophageal...

  • Emerging Concepts of Bile Reflux in the Constellation of Gastroesophageal Reflux Disease. Kauer, Werner K. H.; Stein, Hubert J. // Journal of Gastrointestinal Surgery;Feb2010 Supplement 1, Vol. 14, p9 

    Reflux of gastric and duodenal contents in patients with gastroesophageal reflux disease (GERD) has been postulated as a major cause of complications, such as Barrett’s esophagus or malignant degeneration. We present a summary of experimental, clinical, and immunohistochemical studies...

  • Circadian Variations in Gastric Acid and Pepsin Secretion and Intragastric Bile Acid in Patients with Reflux Esophagitis and in Healthy Controls. Fiorucci, Stefano; Distrutti, Eleonora; Di Matteo, Francesco; Brunori, Paolo; Santucci, Luca; Mallozzi, Ezelino; Bigazzi, Umberto; Morelli, Antonio // American Journal of Gastroenterology;Feb1995, Vol. 90 Issue 2, p270 

    Objectives: Duodenogastric reflux is a physiological phenomenon in both fasting and postprandial state. Because this suggests that bile acids may reflux into the esophagus together with the acid in patients with reflux esophagitis, we investigated the circadian variations of acid and pepsin...

  • Effect of Acid, Pepsin, and Bile Acid on the Stenotic Progression of Traumatized Subglottis. Roh, Jong-Lyel; Yong-Won Lee; Park, Hee T. // American Journal of Gastroenterology;Jun2006, Vol. 101 Issue 6, p1186 

    BACKGROUND AND AIMS: Gastroesophageal reflux disease is related to various laryngeal sequelae. However, there is a lack of established reflux animal models covering longer observation periods. We evaluated the effects of acid, pepsin, and bile acid on healing of the traumatized subglottis in a...

  • The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration. Reder, Nicholas; Davis, Christopher; Kovacs, Elizabeth; Fisichella, P. // Surgical Endoscopy;Jun2014, Vol. 28 Issue 6, p1794 

    Background: Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome after lung transplantation. Unfortunately, the identification of patients with GERD who aspirate still lacks clear diagnostic indicators. The authors hypothesized that...

  • Human sterol 12α-hydroxylase ( CYP8B1) is mainly expressed in hepatocytes in a homogenous pattern. Jin Wang; Greene, Sinead; Eriksson, Lennart; Rozell, Björn; Reihnér, Eva; Einarsson, Curt; Eggertsen, Gösta; Gåfvels, Mats // Histochemistry & Cell Biology;Apr2005, Vol. 123 Issue 4/5, p441 

    The liver is the only organ where the complete synthesis of bile acids takes place. The present study was undertaken to investigate whether regional differences exist within the individual human hepatic lobuli regarding the pattern of expression of sterol 12α-hydroxylase (CYP8B1), a key...

  • Eupatilin attenuates bile acid-induced hepatocyte apoptosis. Park, Su Cheol; Yoon, Jung-Hwan; Kim, Won; Gwak, Geum-Youn; Kim, Kang Mo; Lee, Sung-Hee; Lee, Soo-Mi; Lee, Hyo-Suk // Journal of Gastroenterology;Aug2006, Vol. 41 Issue 8, p772 

    In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics