Dimethylsulfoxide action on fast axoplasmic transport and ultrastructure of vagal axons

Donoso, J. Alejandro; Illanes, Juan-Pablo; Samson, Frederick E.

doi:10.1016/0006-8993(77)90907-6

Cited by 30 publications

(14 citation statements)

References 19 publications

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“…Colchicine, DMSO, and heavy water are all reported to inhibit rapid axonal transport, and this action is believed to reflect their effects on microtubules (Anderson, Edstrom & Hanson, 1972;Donoso, Illanes & Samson, 1976;Grafstein & Forman, 1980). In the present work bidirectional organelle transport was inhibited after about 4 h exposure to 1 mM-colchicine (cf.…”

Section: Agents Which Act On Microtubulessupporting

confidence: 51%

Oscillatory motion of intra‐axonal organelles of Xenopus laevis following inhibition of their rapid transport.

Kendal¹,

Koles²,

Smith³

1983

The Journal of Physiology

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SUMMARY1. The motion of optically detected organelles in myelinated axons of Xenopus laevis was studied in axons bathed in a potassium glutamate based medium and in axons in a similar medium to which various inhibitors ofaxonal transport were added.2. Organelles in the potassium glutamate medium had a motion which was indistinguishable from that previously described for organelles in axons bathed in a conventional physiological saline.3. Colchicine, dimethylsulphoxide, 2,4-dinitrophenol, hyperosmotic solutions, raised concentrations of intracellular calcium ions, and media made up in deuterium oxide caused either a complete or partial inhibition of both anterograde and retrograde organelle transport. 4. When directioned transport had been inhibited by any of the agents used, organelles displayed a longitudinally oriented oscillatory motion.5. An analysis of the variable, or oscillatory, component of organelle motion in axons not treated with inhibitors and in axons in which transport was partially or completely inhibited produced evidence that the dominant frequency components were similar in each case. A maximal estimate of the dominant frequency of oscillatory motion was 0-18+0-02 Hz. The distribution of instantaneous velocities about the mean velocity was not substantially altered as the transport of organelles was inhibited.6. The evidence suggested that the variable component of motion of organelles which show directioned transport is related to the oscillatory motion of organelles whose transport is inhibited.

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Section: Agents Which Act On Microtubulessupporting

confidence: 51%

Oscillatory motion of intra‐axonal organelles of Xenopus laevis following inhibition of their rapid transport.

Kendal¹,

Koles²,

Smith³

1983

The Journal of Physiology

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“…Thirty or more years ago, DMSO (10–15%) was a promising new anti-cancer drug because it induced polymerization and stabilization of microtubules [6], which in turn it was believed, would inhibit mitosis and kill proliferating cancer cells. However, extensive studies of DMSO showed no anti-cancer properties [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Methyl Sulfone Induces Loss of Metastatic Properties and Reemergence of Normal Phenotypes in a Metastatic Cloudman S-91 (M3) Murine Melanoma Cell Line

et al. 2010

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BackgroundThe most deadly form of cancer is not lung or colon, breast or prostate; it is any cancer that has become metastatic. Mortality due to metastatic melanoma, one of the most aggressive and deadly cancers, has increased steadily over the last several decades. Unfortunately, the arsenal of chemotherapeutic agents available today is most often unsuccessful at extending and improving the life expectancy of afflicted individuals. We sought to identify an effective and nontoxic agent against metastatic melanoma.Methodology/Principal FindingsWe chose to study Cloudman S-91 mouse melanoma cells (sub-clone M3, CCL53.1) because these cells are highly aggressive and metastatic, representing one of the deadliest types of cancer. Melanoma cells also had an experimental advantage because their morphology, which is easily monitored, relates to the physiology of metastatic cells and normal melanocytes. We chose to test methyl sulfone as a chemotherapeutic agent for two reasons. Because of its chemical structure, we speculated a potential anti-cancer activity by targeting microtubules. Equally important, methyl sulfone has a well-established safety profile in humans. Surprisingly, we found that malignant melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes characteristic of malignant cells, and the reemergence of phenotypes characteristic of healthy melanocytes. Briefly, over time methyl sulfone induced contact inhibition, loss of ability to migrate through an extracellular matrix, loss of anchorage-independent growth, proper wound healing followed by contact inhibition, irreversible senescence followed by arborization with melanosomes in arbors as seen in normal melanocytes.Conclusions/SignificanceMethyl sulfone may have clinical potential as a non-toxic agent effective against metastatic melanoma. Additionally, methyl sulfone has promise as a tool to explore molecular mechanisms of metastatic transformation as well as fundamental processes such as cell migration, contact inhibition, wound healing and cellular senescence.

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“…For control values, we used the values obtained after injection of the toxin solvent, but these solvents themselves are liable to change nerve metabolism (Donoso et al, 1977;Tashiro and Komya, 1983). Indeed, injection of the solvent alone changes the incorporation of [ 14C]galactose into lipids, compared with saline injection, but it would have been wrong to use as control normal nerves or saline-injected nerves.…”

Section: Discussionmentioning

confidence: 99%

Alteration of axonal microfilaments alters Schwann cell lipid metabolism

Souyri

Maladry-Muller

Bourre

1989

Molecular and Chemical Neuropathology

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To investigate the importance of the neuronal cytoskeleton in Schwann cell metabolism, three agents acting on the microfilaments (cytochalasin D, brevine, and phalloïdin) were injected into the endoneurium of rat sciatic nerve. Sciatic nerves were removed 24 h later and separated into two pieces: the first one was the injection site and the second was from nerves located distal to the injection site. The pieces of nerve were incubated with [14C] galactose for 3 h. At the site of injection, [14C] incorporation into monogalactosyldiacylglycerol (MGDG) was perturbed by the three agents, whereas in the distal part, sulfatides and phosphatidylserine were affected by cytochalasin D and brevine. These results show that the three compounds acting on microfilaments have a different effect on Schwann cell metabolism, depending on whether incubated Schwann cells were directly in contact with the toxin or they were only in contact with the axons affected by the toxin. In the latter case, axonal microfilaments seem to be involved in the regulation of Schwann cell metabolism.

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Dimethylsulfoxide action on fast axoplasmic transport and ultrastructure of vagal axons

Cited by 30 publications

References 19 publications

Oscillatory motion of intra‐axonal organelles of Xenopus laevis following inhibition of their rapid transport.

Oscillatory motion of intra‐axonal organelles of Xenopus laevis following inhibition of their rapid transport.

Methyl Sulfone Induces Loss of Metastatic Properties and Reemergence of Normal Phenotypes in a Metastatic Cloudman S-91 (M3) Murine Melanoma Cell Line

Alteration of axonal microfilaments alters Schwann cell lipid metabolism

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