Nerve growth factor rescue of cisplatin neurotoxicity is mediated through the high affinity receptor: studies in PC12 cells and p75 null mouse dorsal root ganglia.
Nerve growth factor (NGF) rescues dorsal root ganglion neurons and PC12 cells from cisplatin-induced cell death. Two model systems were used to demonstrate that rescue is mediated through the high affinity NGF receptor. In dorsal root ganglion (DRG) neurons isolated from p75(-/-) and control mice, 20 ng/ml NGF completely prevented cisplatin-induced death. In PC12 cells, we overexpressed receptor chimeras between the tumor necrosis factor and NGF receptors. We demonstrated that activation of the intracellular domain of Trk A is responsible for the NGF rescue effect.
Fischer
S J
SJ
Molecular Neuroscience Program, Mayo Graduate and Medical Schools, Rochester, MN 55905, USA.
Podratz
J L
JL
Windebank
A J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D020917:Receptor, trkA / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D020800:Receptor, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D002945:Cisplatin