Melatonin alters the metabolism of the β-amyloid precursor protein in the neuroendocrine cell line PC12

Weihong Song, Debomoy Lahiri

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The deposition of amyloid plaques in brain parenchyma is one of the major pathological hallmarks of Alzheimer's disease (AD). The amyloid in senile plaques is composed of the amyloid β-peptide (Aβ) of 39-43 amino acid residues derived from a larger β-amyloid precursor protein (βAPP). Soluble derivatives of βAPP (sAPP) lacking the cytoplasmic tail, transmembrane domain, and a small portion of the extracellular domain are generated proteolytically by "secretases." Using cell cultures, the authors analyzed the level of sAPP in neuroblastoma and pheochromocytoma (PC12) cells by immunoblotting samples from conditioned media and cell lysates. Normal levels of secretion of sAPP into conditioned media were severely inhibited by treating cells with melatonin (3-4 m M). The inhibitory effect of melatonin on the secretion of sAPP can be reversed. When the cells that were pretreated with melatonin for 10 h were washed, the normal level of secretion of sAPP was restored. Northern blot analyses indicated that the treatment of PC12 cells with melatonin resulted in a significant decrease in the level of mRNA encoding βAPP, β-actin, and glyceraldehyde-3-phosphate dehydrogenase, and that the treatment of a human neuroblastoma cell line with melatonin resulted in no change in levels of these messages. The secretion of sAPP into the conditioned medium was substantially reduced in the differentiated cells similar to reductions observed in melatonin-treated undifferentiated PC12 cells. Melatonin was found to potentiate the nerve growth factor-mediated differentiation in PC12 cells at 24 h. Taken together, these data suggest that melatonin regulates the metabolism of βAPP and other housekeeping genes in a cell-type specific manner, and that melatonin accelerates the early process of neuronal differentiation.

Original languageEnglish
Pages (from-to)75-92
Number of pages18
JournalJournal of Molecular Neuroscience
Volume9
Issue number2
DOIs
StatePublished - Oct 1997

Fingerprint

Neuroendocrine Cells
Amyloid beta-Protein Precursor
Melatonin
Metabolism
Cells
Cell Line
PC12 Cells
Derivatives
Conditioned Culture Medium
Amyloid
Amyloid Plaques
Neuroblastoma
Amyloid Precursor Protein Secretases
Glyceraldehyde-3-Phosphate Dehydrogenases
Essential Genes
Pheochromocytoma
Nerve Growth Factor
Cell culture
Immunoblotting
Northern Blotting

Keywords

  • β-amyloid precursor protein
  • melatonin
  • neuroblastoma cells
  • PC12 cells
  • Pineal gland hormone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Melatonin alters the metabolism of the β-amyloid precursor protein in the neuroendocrine cell line PC12. / Song, Weihong; Lahiri, Debomoy.

In: Journal of Molecular Neuroscience, Vol. 9, No. 2, 10.1997, p. 75-92.

Research output: Contribution to journalArticle

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