Paclitaxel induces axonal microtubules polar reconfiguration and impaired organelle transport: implications for the pathogenesis of paclitaxel-induced polyneuropathy. 2010

Or A Shemesh, and Micha E Spira
Department of Neurobiology, Institute of Life Science, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.

In differentiated axons almost all microtubules (MTs) uniformly point their plus ends towards the axonal tip. The uniform polar pattern provides the structural substrate for efficient organelle transport along axons. It is generally believed that the mass and pattern of MTs polar orientation remain unchanged in differentiated neurons. Here we examined long-term effects of the MTs stabilizing reagent paclitaxel (taxol) over MTs polar orientation and organelle transport in cultured Aplysia neurons. Unexpectedly, we found that rather than stabilizing the MTs, paclitaxel leads to their massive polar reconfiguration, accompanied by impaired organelle transport. Washout of paclitaxel does not lead to recovery of the polar orientation indicating that the new pattern is self-maintained. Taken together the data suggest that MTs in differentiated neurons maintain the potential to be reconfigured. Such reconfiguration may serve physiological functions or lead to degeneration. In addition, our observations offer a novel mechanism that could account for the development of peripheral neuropathy in patients receiving paclitaxel as an antitumor drug.

UI MeSH Term Description Entries
D007091 Image Processing, Computer-Assisted A technique of inputting two-dimensional or three-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer. Biomedical Image Processing,Computer-Assisted Image Processing,Digital Image Processing,Image Analysis, Computer-Assisted,Image Reconstruction,Medical Image Processing,Analysis, Computer-Assisted Image,Computer-Assisted Image Analysis,Computer Assisted Image Analysis,Computer Assisted Image Processing,Computer-Assisted Image Analyses,Image Analyses, Computer-Assisted,Image Analysis, Computer Assisted,Image Processing, Biomedical,Image Processing, Computer Assisted,Image Processing, Digital,Image Processing, Medical,Image Processings, Medical,Image Reconstructions,Medical Image Processings,Processing, Biomedical Image,Processing, Digital Image,Processing, Medical Image,Processings, Digital Image,Processings, Medical Image,Reconstruction, Image,Reconstructions, Image
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D011115 Polyneuropathies Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance. Polyneuropathy, Acquired,Polyneuropathy, Critical Illness,Polyneuropathy, Familial,Polyneuropathy, Inherited,Polyneuropathy, Motor,Acquired Polyneuropathies,Acquired Polyneuropathy,Critical Illness Polyneuropathies,Critical Illness Polyneuropathy,Familial Polyneuropathies,Familial Polyneuropathy,Inherited Polyneuropathies,Inherited Polyneuropathy,Motor Polyneuropathies,Motor Polyneuropathy,Polyneuropathies, Acquired,Polyneuropathies, Critical Illness,Polyneuropathies, Familial,Polyneuropathies, Inherited,Polyneuropathies, Motor,Polyneuropathy
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000972 Antineoplastic Agents, Phytogenic Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. Antineoplastics, Botanical,Antineoplastics, Phytogenic,Agents, Phytogenic Antineoplastic,Botanical Antineoplastics,Phytogenic Antineoplastic Agents,Phytogenic Antineoplastics
D001048 Aplysia An opisthobranch mollusk of the order Anaspidea. It is used frequently in studies of nervous system development because of its large identifiable neurons. Aplysiatoxin and its derivatives are not biosynthesized by Aplysia, but acquired by ingestion of Lyngbya (seaweed) species. Aplysias
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D015388 Organelles Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Organelle
D017239 Paclitaxel A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death. 7-epi-Taxol,Anzatax,Bris Taxol,NSC-125973,Onxol,Paclitaxel, (4 alpha)-Isomer,Paxene,Praxel,Taxol,Taxol A,7 epi Taxol,NSC 125973,NSC125973,Taxol, Bris

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