Picomolar concentrations of hibernation induction delta opioid peptide [D-Ala2,D-Leu5]enkephalin increase the nerve growth factor in NG-108 cells.
The delta opioid peptide [D-Ala2,D-Leu5]enkephalin (DADLE) has been shown to be a neuroprotective agent via mechanisms that are not totally understood. We previously demonstrated that the i.p. injection of DADLE in mice causes an increase of nerve growth factor (NGF) in the brain. To further clarify the NGF-increasing action of DADLE, we examined here the NGF-increasing effect of DADLE in vitro, using cultured NG-108 cells. DADLE dose-dependently increases the immunoreactive level of NGF in NG-108 cells in a bell-shape manner, with the effective DADLE concentrations in the picomolar range (0.01-100 pM). Also, DADLE at 1 pM selectively increases c-Jun and c-Fos, but not c-Rel. These results indicate that DADLE is one of the most potent agents in increasing the NGF in the biological system and that this action of DADLE involves selective increases of c-Jun and c-Fos, transcription factors that promote the NGF expression.
Tsai
Shang-Yi
SY
Cellular Pathobiology Unit/DPS/CNRB, IRP, National Institute on Drug Abuse, NIH/DHHS, Triad Room 3304, 333 Cassell Drive, Baltimore, Maryland 21224, USA.
Hayashi
Teruo
T
Su
Tsung-Ping
TP
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D005910:Glioma; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016308:Enkephalin, Leucine-2-Alanine; D020932:Nerve Growth Factor