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