Effects of chlorpromazine on actin polymerization: slackening of filament elongation and filament annealing.
We have analyzed the effect of chlorpromazine (CPZ) on pure actin. We have found that CPZ quenches Trp-79 and Trp-86 fluorescence and, in agreement with an earlier report on conventional actin, inhibits actin polymerization, lowering the extent of polymerization. Moreover, novel polymerization data are presented indicating that CPZ decreases the maximum polymerization rate in a dose-dependent manner. The assembly inhibition results from the slackening of oligomer formation during the early stages of polymerisation, of filament elongation and of filament annealing. Finally, CPZ strongly inhibits actin filament network formation.
Milzani
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Department of Biology, University of Milan, via Celoria 26, Milan, 20133, Italy.
DalleDonne
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Dalledonne
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D000199:Actins / Q000737:chemistry / Q000187:drug effects* / Q000302:isolation & purification; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000737:chemistry; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan
D000199:Actins; D014364:Tryptophan; D002746:Chlorpromazine