Cytosolic amyloid-{beta} peptide 42 escaping from degradation induces cell death
- Department of Life Science, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712 (Korea, Republic of)
- Department of Biochemistry and Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)
Accumulating evidence suggests that intracellular amyloid-{beta} (A{beta}) peptide triggers the early pathological events in Alzheimer's disease (AD). However, little is known about the consequence of cytosolic A{beta}. In this study, we ectopically expressed A{beta}42 in the cytoplasm of SH-SY5Y neuroblastoma cells by expressing a fusion protein of GFP-tagged ubiquitin and A{beta}42 (GFPUb-A{beta}42). Although GFPUb and A{beta}42 are stochastically produced with the same molar ratio in the cytoplasm, A{beta}42 was completely degraded in more than 50% of the GFPUb-expressing cells. However, if A{beta}42 was not degraded in their cytoplasm, then A{beta}42-expressing cells underwent apoptosis. The number of A{beta}42-expressing cells is significantly increased by the inhibition of proteasome with MG132. Cytosolic A{beta}42 which has escaped degradation inhibits proteasome and thereby may accelerate the accumulation of A{beta}42 and its detrimental effects. Our findings suggest that cells have the potential to degrade A{beta}42 in their cytoplasm but if A{beta}42 appears in the cytoplasm due to its incomplete degradation, it accumulates and may trigger the fatal cascade of pathology of AD.
- OSTI ID:
- 20798980
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 344, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.03.166; PII: S0006-291X(06)00718-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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