Interaction of C-9 aldehydes with microtubular protein in vitro and in cultured cells in the presence of taxol.
Some aldehydes have previously been shown to alter the microtubular system in a concentration-dependent manner. This paper examines the effects of taxol on the impairment of in vitro functionality of microtubular protein and of cytoplasmic microtubules by C-9 aliphatic aldehydes. Taxol-induced polymerization was inhibited by aldehydes in a similar way to GTP-induced polymerization, even though to a different degree. The addition of taxol restored the ability of aldehyde-impaired tubulin to polymerize, but only in the presence of nonanal. Colchicine binding activity in the presence of taxol was slightly modified by aldehydes at 20 degrees C, while it increased at 37 degrees C, compared to controls. Immunofluorescence showed a low disruption of microtubules in fibroblasts incubated with aldehydes and pretreated with taxol, probably as a consequence of its stabilizing activity. Anyway, aldehydes studied behaved differently, indicating a structure-activity relationship.
Department of Experimental Medicine and Oncology, University of Turin, Italy.
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Miglietta
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Olivero
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Gadoni
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Gabriel
D016475:3T3 Cells; D000447:Aldehydes / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003078:Colchicine / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051379:Mice; D008868:Microtubule Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel; D011108:Polymers; D013329:Structure-Activity Relationship; D013696:Temperature; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D000447:Aldehydes; D000470:Alkaloids; D008868:Microtubule Proteins; D011108:Polymers; D014404:Tubulin; C013166:2-nonenal; D006160:Guanosine Triphosphate; C027576:4-hydroxy-2-nonenal; D017239:Paclitaxel; D003078:Colchicine