Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor-mediated endocytosis mechanism
Identifieur interne : 000352 ( France/Analysis ); précédent : 000351; suivant : 000353Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor-mediated endocytosis mechanism
Auteurs : Géraldine Pron [France] ; Nawel Mahrour [France] ; Stéphane Orlowski [France] ; Omar Tounekti [France] ; Bruno Poddevin [France] ; Jean Belehradek [France] ; Lluis M. Mir [France]Source :
- Biochemical Pharmacology [ 0006-2952 ] ; 1998.
English descriptors
- KwdEn :
Abstract
Bleomycin (BLM) does not diffuse through the plasma membrane but nevertheless displays cytotoxic activity due to DNA break generation. The aim of the study was to describe the mechanism of BLM internalisation. We previously provided evidence for the existence of BLM-binding sites at the surface of DC-3F Chinese hamster fibroblasts, as well as of their involvement in BLM cytotoxicity on DC-3F cells and related BLM-resistant sublines. Here we report that A253 human cells and their BLM-resistant subline C-10E also possessed a membrane protein of ca. 250 kDa specifically binding BLM. Part of this C-10E cell resistance could be explained by a decrease in the number of BLM-binding sites exposed at the cell surface with respect to A253 cells. The comparison between A253 and DC-3F cells exposing a similar number of BLM-binding sites revealed that the faster the fluid phase endocytosis, the greater the cell sensitivity to BLM. Moreover, the experimental modification of endocytotic vesicle size showed that BLM cytotoxicity was directly correlated with the flux of plasma membrane area engulfed during endocytosis rather than with the fluid phase volume incorporated. Thus, BLM would be internalised by a receptor-mediated endocytosis mechanism which would first require BLM binding to its membrane receptor and then the transfer of the complex into intracellular endocytotic vesicles, followed by BLM entry into the cytosol, probably from a nonacidic compartment.
Url:
DOI: 10.1016/S0006-2952(98)00282-2
Affiliations:
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ISTEX:B25738CBB23CD3A17B209A6697138874E5A3CABDLe document en format XML
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The aim of the study was to describe the mechanism of BLM internalisation. We previously provided evidence for the existence of BLM-binding sites at the surface of DC-3F Chinese hamster fibroblasts, as well as of their involvement in BLM cytotoxicity on DC-3F cells and related BLM-resistant sublines. Here we report that A253 human cells and their BLM-resistant subline C-10E also possessed a membrane protein of ca. 250 kDa specifically binding BLM. Part of this C-10E cell resistance could be explained by a decrease in the number of BLM-binding sites exposed at the cell surface with respect to A253 cells. The comparison between A253 and DC-3F cells exposing a similar number of BLM-binding sites revealed that the faster the fluid phase endocytosis, the greater the cell sensitivity to BLM. Moreover, the experimental modification of endocytotic vesicle size showed that BLM cytotoxicity was directly correlated with the flux of plasma membrane area engulfed during endocytosis rather than with the fluid phase volume incorporated. Thus, BLM would be internalised by a receptor-mediated endocytosis mechanism which would first require BLM binding to its membrane receptor and then the transfer of the complex into intracellular endocytotic vesicles, followed by BLM entry into the cytosol, probably from a nonacidic compartment.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Gif sur Yvette</li><li>Villejuif</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Pron, Geraldine" sort="Pron, Geraldine" uniqKey="Pron G" first="Géraldine" last="Pron">Géraldine Pron</name></region><name sortKey="Belehradek, Jean" sort="Belehradek, Jean" uniqKey="Belehradek J" first="Jean" last="Belehradek">Jean Belehradek</name><name sortKey="Mahrour, Nawel" sort="Mahrour, Nawel" uniqKey="Mahrour N" first="Nawel" last="Mahrour">Nawel Mahrour</name><name sortKey="Mir, Lluis M" sort="Mir, Lluis M" uniqKey="Mir L" first="Lluis M." last="Mir">Lluis M. Mir</name><name sortKey="Mir, Lluis M" sort="Mir, Lluis M" uniqKey="Mir L" first="Lluis M." last="Mir">Lluis M. Mir</name><name sortKey="Orlowski, Stephane" sort="Orlowski, Stephane" uniqKey="Orlowski S" first="Stéphane" last="Orlowski">Stéphane Orlowski</name><name sortKey="Poddevin, Bruno" sort="Poddevin, Bruno" uniqKey="Poddevin B" first="Bruno" last="Poddevin">Bruno Poddevin</name><name sortKey="Tounekti, Omar" sort="Tounekti, Omar" uniqKey="Tounekti O" first="Omar" last="Tounekti">Omar Tounekti</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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