Erythropoietin protects sensory axons against paclitaxel-induced distal degeneration.
Paclitaxel causes a sensory polyneuropathy with characteristic features of distal axonal degeneration. Although the exact mechanisms underlying distal axonal degeneration are unknown, paclitaxel-induced axonal degeneration has been shown to be associated with an increase in detyrosinated tubulin. Here we show that recombinant human erythropoietin prevents axonal degeneration in sensory neurons in vitro and this effect is associated with downregulation of detyrosinated tubulin. Furthermore, in an animal model of paclitaxel-induced distal sensory polyneuropathy, recombinant human erythropoietin protects against distal axonal degeneration. These findings suggest that recombinant human erythropoietin may be useful as a therapy to prevent paclitaxel-induced sensory polyneuropathy in patients undergoing chemotherapy.
Melli
Giorgia
G
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jack
Christelene
C
Lambrinos
George L
GL
Ringkamp
Mathias
M
Höke
Ahmet
A
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000009:adverse effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D017239:Paclitaxel / Q000009:adverse effects*; D011994:Recombinant Proteins; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D014404:Tubulin; D004921:Erythropoietin; D014443:Tyrosine; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol