Al3+-mediated changes in membrane physical properties participate in the inhibition of polyphosphoinositide hydrolysis

Sandra V. Verstraeten, Patricia I. Oteiza

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

We investigated the possible involvement of Al3+-induced alterations in membrane physical properties in Al3+-mediated inhibition of polyphosphoinositide (PPI) hydrolysis by the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC). Liposomes composed of brain phosphatidylcholine (PC) or of PC and a mixture of brain PPI (PC:PPI) were incubated in the presence of Al3+ (1-100μM). We evaluated: (1) the amount of membrane-bound Al3+, (2) the effects of Al3+ on key membrane physical properties (surface potential, lipid fluidity, and lipid arrangement), and (3) the hydrolysis of PPI. Al3+ binding to PC:PPI (60:40 mol/mol) liposomes was 1.3 times higher than to PC:PPI (90:10 mol/mol) liposomes and did not change after treatment with Triton X-100. Al3+ increased membrane surface potential, promoted the loss of membrane fluidity, and caused lateral phase separation in PC:PPI liposomes. Phosphatidylinositol and phosphatidylinositol monophosphate hydrolysis in the presence of PI-PLC was not affected by Al3+, but a significant and concentration-dependent inhibition of PIP2 hydrolysis was observed, an effect that was prevented by previous bilayer disruption with Triton X-100. The obtained results support the hypothesis that Al3+ binding to liposomes promotes the formation of rigid clusters enriched in PPI, restricting the accessibility of the enzyme to the substrate and subsequently inhibiting PIP2 hydrolysis by PI-PLC.

Original languageEnglish (US)
Pages (from-to)263-271
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume408
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Aluminum
  • Brain phospholipase C-phosphatidylinositol specific
  • Lipid signaling
  • Neurotoxicity
  • Phosphoinositides
  • PIP

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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