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Mechanism of chlorotoxin-induced chloride channel internalisation in glioma cells Kamal Rayees, Abdul Azeez (1), Nadia, Adotevi (1), Peter N, Strong


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Mechanism of chlorotoxin-induced chloride channel internalisation in glioma cells
Kamal Rayees, Abdul Azeez (1), Nadia, Adotevi (1), Peter N, Strong (1), Kirsti A, Newton (1)
Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK. (1)



  1. Glioma is a highly invasive cancer with generally poor prognosis. Chlorotoxin (a

  2. neurotoxin found in the venom of the scorpion Leiurus quinquestriatus) (1)

  3. prevents shrinkage of glioma cells, and therefore restricts their invasiveness. The

  4. toxin is believed to exert its physical effect via lipid raft-mediated toxin

  5. internalisation from the glioma cell surface. One key member of the raft complex

  6. is thought to be matrix metalloproteinase-2 (MMP-2) (2). We are studying toxin-

  7. MMP interaction as a potential mechanism of internalisation. Chlorotoxin binds to

  8. and inhibits MMP-2 (3). We have demonstrated that both crude Leiurus

  9. quinquestriatus venom and chlorotoxin inhibit MMP-1 (collagenase) activity by

  10. using an enzyme assay incorporating a fluorescent substrate. Since chlorotoxin

  11. inhibits MMP-1 activity we suggest that expression of collagenase as well as

  12. gelatinase is involved in chloride channel internalisation and therefore the ability

  13. of chlorotoxin to inhibit cell shrinkage as a consequence of channel

  14. internalisation.


References
(1) DeBin, J.A. et al. (1993) Am J Physiol Cell Physiol 264: C361-C369

(2) Sontheimer, H (2008) Exp Biol Med 233: 779-791

(3) Deshane, J et al (2003) J Biol Chem 278: 4135-4144


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