Microtubule disruption

Step 8 Retrograde transport occurs to restart the cycle. This last step may retrieve certain proteins or recycle v-SNAREs. Nocodazole, a microtubule-disrupting agent, inhibits this step. 

While ionophore-stimulated 5-LO product release from neutrophils is often used as an indication of 5-LO inhibition, one must interpret these results cautiously. For example, halothane, an inhalation anaesthetic which may cause membrane perturbation [26], and colchicine, a microtubule disrupter [27], both were active, but presumably not because of 5-LO inhibition. A23187 is assumed to stimulate 5-LO by raising the intracellular calcium level, but this agent causes many other effects which may or may not be related to 5-LO activation, including changes in membrane potential, protein phosphorylation, phospholipid turnover, cyclic nucleotide levels, and DNA and protein synthesis [28]. Also, the effects of some putative 5-LO inhibitors on product release from neutrophils has been shown to vary with the stimulant used [29]. 

Cytoskeletal elements may also be involved in mediating the effects of prolactin on the mammary gland. Colchicine, which disrupts intracellular microtubules, completely blocks the effect of prolactin on casein mRNA production [86]. However, griseofulvin, another microtubule-disrupting drug, has no such effect. 

Drewes G, Ebneth A, Preuss U, Mandelkow EM, MandeUcow E (1997) MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell 89 297-308. 

Benomyl is a microtubule-disrupting agent in fungi. This agent may cause chromosomal aberrations (e.g., aneuploidy). There is very little evidence of benomyl toxicity in mammals, however. Benomyl itself does not have any direct effect on acetylcholinesterase. Under certain conditions, however, benomyl breaks down to produce carbendazim and butyl isocyanate, of which the isocyanate is an irreversible inhibitor of acetylcholinesterase with comparable potency to some active organophosphorus inhibitors. 

Historically, insight into the role of Sertoli cell microtubules in promoting spermatogenesis has been gleaned from analyzing the actions of known microtubule disrupters in the testis. Both colchicine and taxol lead to defects in spermiation and residual body elimination, activities attributed to Sertoli cells (105-107). Because microtubules are present in all cells, however, these studies cannot rule out potential actions on other cellular targets, particularly on the germ cells themselves. 

Russell LD, Malone IP, MacCurdy DS. 1981. Effect of the microtubule disrupting agents, colchicine and vinblastine, on seminiferous tubule structure in the rat. Tissue Cell 13 349-67... 

These studies established that (a) the microtubules of the R biotype are hyperstabilized and (b) phenocopies of the R biotype in structure and in insensitivity to microtubule disrupters could be induced by treating the S biotype with taxol. From this, one could conclude that a major factor in dinitroaniline-resistance in Eleusine is the hyperstability, presumably caused by the novel 0-tubulin form in the R biotype. This does not eliminate the possibility that the binding of dinitroaniline herbicides is altered in the R biotype and we hope to investigate this possibility as well. 

O Boyle NM, Greene LM, Keely NO, Wang S, Cotter TS, Zisterea- DM, Meegan MJ (2013) Synthesis and biochemical activities of antiproliferative amino acid and phosphate derivatives of microtubule-disrupting beta-lactam combretastatins. Eur J Med Chem 62 705-721... 

There is increasing evidence that the microtubules are an important component in the interaction between the cytoskeleton and specific mRNAs. Microtubule preparations have been found to contain ribosomes and polysomes (Hamill et al. 1994) and inhibitor studies showed that mRNA localisation in oocytes is sensitive to colchicine (Yisraeli et al. 1990, POKRYWKA and Stephenson 1994). A cyto-skeletal fraction from Drosophila oocytes is enriched in bicoid mRNA, and this mRNA is released by microtubule-disrupting agent colchicine (Pok-RYWKA and Stephenson 1994). 

Yang, W., and Storrie, B. (1998). Scattered Golgi elements during microtubule disruption are initially emiched in trans-Golgi proteins. Mol Biol. Cell 9,191-207. 

Sugimoto K., Himmelspach R., Williamson R.E., and Wasteneys G.O. 2003. Mutation or drug-dependent microtubule disruption causes radial swelling without altering parallel cellulose microfibril deposition in Arabidopsis root cells. The Plant Cell 15 1414-1429. 

Colchicine with its microtubule-disrupting properties limits the chemotactic and phagocytic activity of polymorphonuclear lymphocytes. It also induces the release of prostaglandin E, a suppressor of leukocyte function by increasing the level of cyclic adenosine monophosphate [39]. Furthermore, the ability of colchicine in inhibition of IL-1 production and histamine release makes it an excellent drug for a number of dermatitis-related complexities like psoriasis, Behget s syndrome, recurrent aphthous stomatitis, leukocytoclastic vasculitis and urticarial vasculitis, bullous disease, scleroderma, fibromatosis. Sweet s syndrome, amyloidosis, and many more [40]. 

Miura K, Imura N (1989) Mechanism of cytotoxicity of methylmercury, with special reference to microtubule disruption. Biol Trace Elem Res 21 313-315 Miura K, Suzuki K, Imura N (1978) Effects of methylmercury on mitotic mouse glioma cells. Environ Res 17 453-471... 

JNKs can be activated by a large range of different stimuli, including kainic acid [47], microtubule-disrupting agents [48], double-stranded ribonucleic acid (RNA) [49], viral infections [49], tumor necrosis factors, interleukins [50], osmotic stress [51], and trophic factor withdrawal [30]. JNKs have also been reported to be activated by oxidative stress, particularly that induced by ultraviolet radiation [47], hypoxia [52], ischemia [53], hydrogen peroxide [30,54], peroxynitrite [55], malondialdehyde [56], and 4-hydroxynonenal [57]. 

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