Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: Implications for Alzheimer's disease

Alessandra Castegna, Christopher M. Lauderback, Hafiz Mohmmad-Abdul, D. Allan Butterfield

Research output: Contribution to journalArticle

Abstract

Membrane lipid bilayer asymmetry is maintained by the ATP-dependent enzyme flippase. An early signal of synaptosomal apoptosis is the loss of phospholipid asymmetry and the appearance of phosphatidylserine (PS) in the outer leaflet of the membrane. Two highly reactive products of lipid peroxidation, 4-hydroxynonenal (HNE) and acrolein, both elevated in Alzheimer's disease (AD) brain, have been shown to induce apoptosis and disrupt cellular ion homeostasis. These reactive aldehydes can structurally modify proteins by covalent interaction and inhibit enzyme function. Phospholipid asymmetry of PS is maintained by the ATP-requiring enzyme flippase. We have investigated the inactivation of the transmembrane enzyme aminophospholipid-translocase (or flippase) by HNE and acrolein. Flippase activity depends on a critical cysteine residue, a possible site of covalent modification by HNE or acrolein. The present study demonstrates that these alkenals induce the appearance of PS on the outer bilayer lamellae and suggests that increases in intracellular Ca 2+ might not be the sole cause for loss of flippase activity. Rather, other mechanisms that could modulate the function of flippase might be important in phospholipid asymmetry disruption. These results are discussed with potential relevance to neuronal loss in Alzheimer's disease brain.

Original languageEnglish
Pages (from-to)193-197
Number of pages5
JournalBrain Research
Volume1004
Issue number1-2
DOIs
Publication statusPublished - Apr 9 2004

Keywords

  • Alzheimer's disease
  • Degenerative disease: Alzheimer's - miscellaneous
  • Disorders of the nervous system
  • Flippase
  • HNE
  • Lipid asymmetry
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: Implications for Alzheimer's disease'. Together they form a unique fingerprint.

  • Cite this