Bile acid induces hydrophobicity-dependent membrane alterations

Sandeep Akare, Jesse D. Martinez

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Elevated concentrations of fecal bile acids are a known risk factor for colon cancer, owing to alterations in cellular signaling. In colonic cells, where bile acid uptake is minimal, the hydrophobicity-induced membrane perturbation and alterations have been proposed, but these membrane alterations are largely uncharacterized. In this study, we examined the determinants and characteristics of bile acid-induced membrane alterations, utilizing PKCα activation and cholesterol up-regulation as model indicators. We found that bile acid-induced PKCα activation is a function of hydrophobicity and correlated with alteration in membrane lipid composition, as evident by the significant up-regulation in membrane cholesterol and phospholipid. We found that bile acid do not cause cell membrane disruption at a concentration sufficient to activate PKCα, but do induce drastic alterations in membrane composition. Bile acid also induced the modification and up-regulation of caveolin-1 in a hydrophobicity-dependent manner, implying widespread receptor dysregulation. Similarly, ERK1/2 activation was observed only in response to hydrophobic bile acids, suggesting hydrophobicity-induced caveolar or membrane stress. Experiments with sodium lauryl sarcosine and cholesteryl hemisuccinate showed that bile acid-induced membrane alterations can be mimicked by hydrophobic molecules unrelated to bile acids, strongly implicating hydrophobicity as an important determinant of bile acid signaling.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1735
Issue number1
DOIs
StatePublished - Jun 15 2005

Keywords

  • Bile acid hydrophobicity
  • Caveolin
  • Cholesterol
  • Colon cancer
  • Membrane alteration
  • PKCα

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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