title: Theonezolide A, a novel marine macrolide, induces drastic shape change in rabbit platelets by reorganization of microtubules.
abstract: Theonezolide A, a marine macrolide, and thrombin caused a shape change followed by an aggregation in the rabbit platelets. Theonezolide A-induced platelet shape change, estimated by a decrease in light transmission, appeared to a greater extent than thrombin-induced one. Morphological studies using an electron microscope showed that theonezolide A changed platelet shape with various numbers of long pseudopods, loosing their discoid shape. Theonezolide A-induced shape change was inhibited by a microtubule-stabilizing agent, taxol, but not by an actin-depolymerizing agent, cytochalasin B. In contrast, thrombin-induced shape change was inhibited by cytochalasin B but not by taxol. Confocal fluorescence microscopy showed that circumferential microtubule bundle disappeared in the platelets treated with theonezolide A. Theonezolide A had no direct effect on polymerization of microtubules isolated from bovine brain, indicating that it indirectly causes microtubule reorganization. These results suggest that theonezolide A induces drastic shape change through reorganization of microtubules in rabbit platelets. Thus, theonezolide A is a useful drug to examine microtubule reorganization in the cells.
authors.affiliation: Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Mitsui-Saito
authors.forename: Satoko
authors.initials: S
authors.lastname: Ohkubo
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Obara
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Yanagisawa
authors.forename: Jun'Ichi
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohizumi
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure*; D048429:Cell Size / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D066298:In Vitro Techniques; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008868:Microtubule Proteins / Q000737:chemistry / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D010080:Oxazoles / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D018942:Macrolides; D008868:Microtubule Proteins; D010080:Oxazoles; D013844:Thiazoles; C104930:theonezolide A; D003571:Cytochalasin B; D013917:Thrombin; D017239:Paclitaxel