Effect of alkaline pH on taxol-microtubule interactions.
Taxol stabilizes microtubules against the depolymerizing effects of cold temperature, drugs and Ca++. In this report, the effect of alkaline pH on microtubules polymerized in the presence of taxol has been studied. Although taxol-microtubules are more stable than microtubules assembled in the presence of GTP, taxol-microtubules can be partially disassembled when the pH becomes more alkaline. A portion of the recovered tubulin dimer is assembly competent upon pH adjustment to approximately 6.6 and the microtubules formed upon the induction of assembly by GTP are normal as judged by electron microscopy. The data indicate that alkaline pH can be used to recover assembly-competent tubulin from a taxol-microtubule complex. At pH 6.6, taxol-induced polymers consisted of two components. The majority were microtubules, but in addition hoops and ribbons were also present. At alkaline pH, the microtubules were more stable than the hoops and ribbons and at pH greater than 7.5 they were the only stable structures. Microtubules stabilized by taxol are protected against the depolymerizing action of podophyllotoxin even at alkaline pH, whereas the hoops and ribbons are depolymerized.
Ringel
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Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York.
Horwitz
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SB
D000470:Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002417:Cattle; D006863:Hydrogen-Ion Concentration; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel; D011485:Protein Binding; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel