Effect of ionophores on the processing of the β-amyloid precursor protein in different cell lines

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12 Scopus citations

Abstract

1. Alzheimer's disease is characterized by the deposition in the brain of extracellular amyloid plaques and vascular deposits consisting mostly of amyloid β-peptide (A β). A β, a polypeptide of 39-43 amino acids (Mr, ∼4 kDa), is derived proteolytically from a family of proteins of 695-770 amino acids (Mr, ∼110-140 kDa) called β-amyloid precursor protein (βAPP). 2. βAPP, an integral membrane glycoprotein, is extensively posttranslationally modified within the endoplasmic reticulum (ER) and various Golgi compartments. βAPP is cleaved by proteases in either the trans-Golgi network or the post-Golgi apparatus and then secreted as a truncated soluble form into the conditioned media of cultured cells and cerebrospinal fluid samples from human subjects. βAPP can be processed either by an antiamyloidogenic secretory pathway or by an endosomal/lysosomal pathway. 3. I studied the effect of two ionophores on the processing of βAPP in cultured cells. Monensin and, in some cases, ammonium chloride increase the intracellular accumulation of βAPP in several cell lines and may alter its processing. Monensin, which had the most consistent effects, also inhibited secretion of βAPP in a differentiated (growth factor mediated) cell line. Nigericin, with greater K+ selectivity, was less able to alter the accumulation and possible processing of the protein. 4. These results suggest that the increase in the accumulation of intracellular βAPP observed after treating cells with ionophores has some specificity. The selective effect of these ionophores on the metabolism of βAPP may provide a model system to analyze the pathways for studying maturation, secretion, and degradation of βAPP.

Original languageEnglish (US)
Pages (from-to)297-313
Number of pages17
JournalCellular and Molecular Neurobiology
Volume14
Issue number4
DOIs
StatePublished - Aug 1 1994

Keywords

  • amyloid β-peptide
  • Golgi apparatus
  • monensin
  • nigericin
  • protein processing
  • protein transport

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

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