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

Neurosci Lett. 2001 Jul 27;308(1):1-4. doi: 10.1016/s0304-3940(01)01956-5.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / antagonists & inhibitors*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cisplatin / antagonists & inhibitors*
  • Cisplatin / toxicity
  • Dose-Response Relationship, Drug
  • Drug Interactions / genetics
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • Nerve Growth Factor / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells / cytology
  • PC12 Cells / drug effects
  • PC12 Cells / metabolism
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / physiopathology
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / physiology
  • Rats
  • Receptor, Nerve Growth Factor / deficiency*
  • Receptor, Nerve Growth Factor / genetics
  • Receptor, trkA / drug effects*
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antineoplastic Agents
  • Neuroprotective Agents
  • Receptor, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Nerve Growth Factor
  • Receptor, trkA
  • Cisplatin