DARP-36aa selectively promotes survival and morphological development of cultured mesencephalic neurons.

Abstract

We examined the effects of DARP-36aa on the survival and morphological development of embryonic rat mesencephalic neurons. Treatment of mesencephalic cultures with DARP-36aa, a synthetic peptide corresponding to the N terminal of dopamine-releasing protein (DARP), resulted in a 1.8-fold increase in neuron survival. Morphological analysis revealed that DARP-36aa-treated neurons contained 48% more branching points per neuron compared with controls. DARP-36aa selectively affected mesencephalic cultures; diencephalic and C6 glioma cells were not affected by DARP-36aa treatments. Mesencephalic cultures were also incubated with polyclonal antibodies against DARP-36aa (anti-DARP-36aa) to assess the effect of immunoneutralization of endogenous DARP on these cells. Mesencephalic cultures treated with anti-DARP-36aa contained 43% fewer neurons, and the number of branching points per neuron was decreased by nearly twofold compared with cultures grown with medium alone. Similar to cultures treated with DARP-36aa, immunoneutralization of DARP had no effect on any parameters examined in primary diencephalic and C6 glioma cultures. Mesencephalic cultures maintained in the presence of DARP-36aa had a 3.2-fold increase in the number of tyrosine hydroxylase (TH)-immunoreactive neurons, whereas anti-DARP-36aa incubations decreased TH-immunoreactive neurons by 40% compared with control cultures. Finally, coincubation of the specific tyrosine kinase inhibitor genistein with DARP-36aa resulted in a complete attenuation of DARP-36aa-mediated neuron survival and development in mesencephalic cultures. The findings indicate that DARP-36aa is a novel neurotrophic peptide that selectively promotes the survival and development of mesencephalic neurons.

• Authors: Sean M Smith, Victor D Ramirez
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 23 Issue 1 Pg. 252-9 (Jan 01 2003) ISSN: 1529-2401 [Electronic] United States
• PMID: 12514222 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Catecholamines
• DARP-36aa
• Enzyme Inhibitors
• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Peptide Fragments
• dopamine-releasing factor, rat
• Genistein
• Tyrosine 3-Monooxygenase

Topics

• Amino Acid Sequence
• Animals
• Antibodies (pharmacology)
• Catecholamines (metabolism)
• Cell Count
• Cell Survival
• Cells, Cultured
• Diencephalon (cytology, embryology)
• Enzyme Inhibitors (pharmacology)
• Genistein (pharmacology)
• Glycoproteins (chemistry)
• Intercellular Signaling Peptides and Proteins
• Mesencephalon (cytology, embryology)
• Molecular Sequence Data
• Nerve Tissue Proteins (chemistry, immunology, pharmacology)
• Neurons (cytology, drug effects)
• Peptide Fragments (chemistry, immunology, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Tumor Cells, Cultured
• Tyrosine 3-Monooxygenase (analysis)