Effect of drugs affecting microtubular assembly on microtubules, phospholipid synthesis and physiological indices (signalling, growth, motility and phagocytosis) in Tetrahymena pyriformis.
Structural changes of microtubules, incorporation of radioactively labelled components into phospholipids, cell motility, growth and phagocytosis were studied under the effect of four drugs affecting microtubular assembly: colchicine, nocodazole, vinblastine and taxol. Although the first three agents influence microtubules in the direction of depolymerization and the fourth stabilizes them, their effects on the structure of microtubules cannot be explained by this. Using confocal microscopy after an acetylated anti-tubulin label, in nocodazole- and colchicine-treated cells, the basal body cages disappear and longitudinal microtubules (LM) became thinner without changing transversal microtubules (TM). After taxol treatment LM also became thinner, however TM disappeared. Under the effect of vinblastine TM became thinner, without influencing LM. These drugs influence the incorporation of components ([(3)H]-serine, [(3)H]-palmitic acid and (32)P) into phospholipids, however their effect is equivocal and cannot be consequently coupled with the effect on the microtubules. Nocodazole, vinblastine and taxol significantly reduced the cell's motility, however colchicine did so to a lesser degree. Vinblastine and nocodazole totally inhibited, and taxol significantly decreased cell growth, while colchicine in a lower concentration increased the multiplication of cells. Phagocytosis was not significantly influenced after 1 min, but after 5 min all the agents studied (except colchicine) significantly inhibited phagocytosis. After 15 and 30 min each molecule caused highly significant inhibition. The experiments demonstrate that drugs affecting microtubular assembly dynamics influence differently the diverse (longitudinal, transversal etc.) microtubular systems of Tetrahymena and also differently influence microtubule-dependent physiological processes. The latter are more dependent on microtubular dynamics than are changes in phospholipid signalling.
Kovács
P
P
Department of Genetics, Semmelweis University, Cell and Immunobiology, Budapest, Hungary. kovpet@net.sote.hu
Csaba
G
G
D000107:Acetylation; D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism*; D009068:Movement / Q000187:drug effects / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D019308:Palmitic Acid / Q000493:pharmacokinetics; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D010743:Phospholipids / Q000096:biosynthesis; D010761:Phosphorus Radioisotopes; D012694:Serine / Q000493:pharmacokinetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D014316:Tritium; D014404:Tubulin / Q000276:immunology / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D010743:Phospholipids; D010761:Phosphorus Radioisotopes; D014404:Tubulin; D014316:Tritium; D019308:Palmitic Acid; D012694:Serine; D014747:Vinblastine; D017239:Paclitaxel; D015739:Nocodazole; D003078:Colchicine