title: Mitoxantrone changes spectrin-aminophospholipid interactions.
abstract: Understanding drug-membrane and drug-membrane protein interactions would be a crucial step towards understanding the action and biological properties of anthracyclines, as the cell membrane with its integral and peripheral proteins is the first barrier encountered by these drugs. In this paper, we briefly describe mitoxantrone-monolayer and mitoxantrone-bilayer interactions, focusing on the effect of mitoxantrone on the interactions between erythroid or nonerythroid spectrin with phosphatidylethanolamine-enriched mono- and bilayers. We found that mitoxantrone markedly modifies the interaction of erythroid and nonerythroid spectrins with phosphatidylethanolamine/phosphatidylcholine (PE/PC) monolayers. The change in delta pi induced by spectrins is several-fold larger in the presence of 72 nM mitoxantrone than in its absence: spectrin/mitoxantrone complexes induced a strong compression of the monolayer. Spin-labelling experiments showed that spectrin/mitoxantrone complexes caused significant changes in the order parameter measured using a 5'-doxyl stearate probe in the bilayer, but they practically did not affect the mobility of 16'-doxyl stearate. These results indicate close-to-surface interactions/penetrations without significant effect on the mid-region of the hydrophobic core of the bilayer. The obtained apparent equilibrium dissociation constants indicated relatively similar mitoxantrone-phospholipid and mitoxantrone-spectrin (erythroid and nonerythroid) binding affinities. These results might in part, explain the effect of mitoxantrone on spectrin distribution in the living cells.
authors.affiliation: Institute of Biochemistry and Molecular Biology, University of Wrocław, Wrocław, Poland.
authors.forename: Patrycja M
authors.initials: PM
authors.lastname: Dubielecka
authors.forename: Anna
authors.initials: A
authors.lastname: Trusz
authors.forename: Witold
authors.initials: W
authors.lastname: Diakowski
authors.forename: Michał
authors.initials: M
authors.lastname: Grzybek
authors.forename: Anna
authors.initials: A
authors.lastname: Chorzalska
authors.forename: Bozena
authors.initials: B
authors.lastname: Jaźwiec
authors.forename: Marek
authors.initials: M
authors.lastname: Lisowski
authors.forename: Adam
authors.initials: A
authors.lastname: Jezierski
authors.forename: Aleksander F
authors.initials: AF
authors.lastname: Sikorski
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D004910:Erythrocyte Membrane / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D013049:Spectrin / Q000378:metabolism*; D013113:Spin Labels
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D013113:Spin Labels; D013049:Spectrin; C483858:phosphatidylethanolamine; D008942:Mitoxantrone