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Amyloid precursor protein binding protein Fe65 is cleaved by caspases during DNA damage-induced apoptosis

Kazunori Saeki1, Yasuyo Nose, Nobukuni Hirao

  • 1Department of Biochemistry, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278–8510, Japan.

Biological & Pharmaceutical Bulletin
|March 19, 2011
PubMed

Insights

Fe65 protein is cleaved during DNA damage-induced apoptosis in neuronal cells. This caspase-mediated cleavage provides new insights into amyloid-beta production and neuronal cell death in Alzheimer's disease.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Apoptosis is a crucial process in cell death, executed by caspases that cleave cellular proteins.
  • Identifying new caspase substrates can elucidate novel apoptosis signaling pathways.
  • Fe65, an amyloid precursor protein (APP) binding protein, plays a role in APP processing.

Purpose of the Study:

  • To investigate if Fe65 is proteolytically degraded during DNA damage-induced apoptosis in neuronal cells.
  • To explore the role of caspases in Fe65 cleavage.
  • To understand the implications of Fe65 cleavage in Alzheimer's disease pathogenesis.

Main Methods:

  • Utilized human neuroblastoma SH-SY5Y cells, a neuron-like cell line.
  • Induced apoptosis using DNA damaging agents: etoposide (ETP) and camptothecin (CPT).
  • Assessed Fe65 cleavage and caspase activation (caspase-9, caspase-3) using Western blotting and caspase inhibitors (z-VAD-fmk).

Main Results:

  • DNA damaging agents induced dose-dependent apoptosis in SH-SY5Y cells.
  • Fe65 (97 kDa) was cleaved into a 65 kDa product during apoptosis.
  • Fe65 cleavage was dependent on caspase activation and inhibited by a pan-caspase inhibitor.

Conclusions:

  • Fe65 undergoes caspase-mediated cleavage during DNA damage-induced apoptosis.
  • This cleavage provides a potential link between DNA damage, Fe65 function, and amyloid-beta (Aβ) production.
  • Findings offer new insights into the molecular mechanisms underlying Aβ production and neuronal cell death in Alzheimer's disease.

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