Related Experiment Video

Updated: Aug 9, 2026

Ileectomy-induced Bile Overaccumulation in Mouse Intestine
06:55

Ileectomy-induced Bile Overaccumulation in Mouse Intestine

Published on: August 21, 2017

Deoxycholic acid induces intracellular signaling through membrane perturbations

Samira Jean-Louis1, Sandeep Akare, M Ahad Ali

  • 1Cancer Biology Interdisciplinary Program, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.

The Journal of Biological Chemistry
|March 21, 2006
PubMed

Insights

Secondary bile acids like deoxycholic acid (DCA) promote colon tumors by altering cell membrane structure. DCA disrupts cholesterol distribution and activates signaling pathways, initiating tumor promotion via membrane changes.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Gastroenterology

Background:

  • Secondary bile acids are implicated in colon tumor promotion.
  • The precise mechanisms underlying bile acid-induced tumor promotion remain largely unknown.
  • Understanding bile acid interactions at the cellular level is crucial for cancer research.

Purpose of the Study:

  • To investigate the molecular mechanisms by which secondary bile acids affect cell membrane structure and function.
  • To elucidate the role of cholesterol and membrane microdomains in bile acid-induced cellular signaling.
  • To compare the effects of different bile acids, specifically deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA).

Main Methods:

  • Cell treatment with methyl-beta-cyclodextrin to deplete cholesterol.
  • Filipin staining to visualize cholesterol redistribution.
  • Analysis of caveolin-1 distribution in membrane microdomains.
  • Fluorescence anisotropy to measure membrane fluidity.
  • Use of radiolabeled bile acids to track localization.
  • Assessment of tyrosine phosphorylation and epidermal growth factor receptor (EGFR) activation.

Main Results:

  • Deoxycholic acid (DCA) perturbs membrane structure by altering cholesterol distribution and membrane microdomains.
  • DCA treatment leads to decreased membrane fluidity and affects caveolin-1 localization.
  • Bile acids interact with and localize to microdomains based on their physicochemical properties.
  • DCA induces ligand-independent activation of epidermal growth factor receptor (EGFR) and tyrosine phosphorylation.
  • Ursodeoxycholic acid (UDCA) did not induce these signaling effects despite microdomain interaction.

Conclusions:

  • Bile acid-induced cellular signaling, potentially leading to colon tumor promotion, is initiated by alterations in plasma membrane structure.
  • Cholesterol redistribution within membrane microdomains is a key early event in DCA-mediated signaling.
  • The specific physicochemical properties of bile acids determine their ability to modulate membrane structure and activate signaling pathways.

More Related Videos

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport08:42

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Published on: November 27, 2016

Real Time Monitoring of Intracellular Bile Acid Dynamics Using a Genetically Encoded FRET-based Bile Acid Sensor09:21

Real Time Monitoring of Intracellular Bile Acid Dynamics Using a Genetically Encoded FRET-based Bile Acid Sensor

Published on: January 4, 2016

Related Concept Videos

Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
Lipid Absorption01:24

Lipid Absorption

Dietary triglycerides from chyme in the duodenum are mixed with bile salts produced by the liver to emulsify fats. As a result, large droplets are broken down into smaller ones, increasing the surface area for enzymatic action. Once emulsified, pancreatic lipases hydrolyze the triglycerides into free fatty acids and monoglycerides.
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...