Different effects of vinblastine on the polymerization of isotypically purified tubulins from bovine brain

Israr A. Khan, Richard F. Ludueña

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Vinblastine, a highly successful antitumor drug, targets the tubulin molecule. Tubulin, the subunit protein of microtubules, consists of an α- and a β-subunit, both of which consist of isotypes encoded by different genes. We have purified three isotypes of bovine brain tubulin, namely, αβII, αβIII and αβIV. Microtubule associated protein-2 (MAP2) and Tau-induced assembly of these isotypes were compared in the presence and absence of vinblastine. MAP2-induced assembly of unfractionated tubulin and all the isotypes except αβII tubulin was resistant to 1 μM vinblastine. Vinblastine at low concentrations (< 10 μM) progressively inhibited the assembly of all of the isotypes but the vinblastine concentration required for inhibition of MAP2-induced microtubule assembly was minimal for αβII. The tau-induced assembly of unfractionated tubulin and αβIII were equally sensitive to 1 μM vinblastine whereas αβII and αβIV were much more sensitive to vinblastine. The microtubules obtained in the presence of tau from unfractionated tubulin, αβII and αβIV could be easily aggregated by 20 μM vinblastine whereas such as aggregation of microtubules obtained from αβIII and tau required approximatedly 40 μM vinblastine. Our results suggest that among the tubulin isotypes, αβIII is the most sensitive to vinblastine in the presence of MAPs while αβIII is the most resistant and this intrinsic resistance of αβII dimers persists in the polymeric form of αβIII tubulin as well. These results may be relevant to the therapeutic and toxic actions of vinblastine.

Original languageEnglish (US)
Pages (from-to)3-13
Number of pages11
JournalInvestigational New Drugs
Volume21
Issue number1
DOIs
StatePublished - Feb 1 2003

Keywords

  • Microtubules
  • Tubulin
  • Tubulin isotypes
  • Vinblastine
  • Vinca alkaloids

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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