Menadione-induced cytotoxicity effects on human erythrocyte membranes studied by electron paramagnetic resonance

Chafia H. Trad, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Menadione (2-methyl-1,4-naphtoquinone) is cytotoxic to hepatocytes. In order to begin to investigate the changes in the physical state of membranes induced by this cytotoxic substance, electron paramagnetic resonance (EPR) spin-labeling techniques were used in conjunction with spin labels specific for cytoskeletal proteins, bilayer lipids, or cell-surface sialic acid or galactose to investigate erythrocyte membranes. We studied the molecular effects of oxidation of 200 μM menadione on the different membrane domains. The major findings are: (1) menadione increases protein-protein interactions p < 0.001 of cytoskeletal proteins, (2) there is a slightly significant increase in the rotational motion of spin-labeled sialic acid (P < 0.05), while (3) the physical state of galactose residues was unaffected by menadione. Since glycophorin is coupled to the major cytoskeletal protein, spectrin, by protein 4.1, we suggest that menadione-indueed oxidation could alter the conformation of protein 4.1. As a consequence, single or multiple sites of weakness could be induced leading to the alteration of the interactions of the cytoskeletal network and its anchoring domains in the membrane. These results are discussed with reference to possible mechanisms involved in the cytotoxic action of menadione.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
JournalToxicology Letters
Issue number2
StatePublished - Aug 1994

Bibliographical note

Funding Information:
This work was supportedin part by grantsf rom NSF (EHR-9108764a) nd NIH (AG-10836)t o D.A. Butterfield.C .H. Trad was supportedb y the BOBST Travel Grant from the AmericanU niversity of Beirut.


  • Band 4.1
  • Cytoskeletal proteins
  • Erythrocyte membranes
  • Menadione
  • Oxidation
  • Sialic acid
  • Spin labeling

ASJC Scopus subject areas

  • Toxicology


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