Premium
Proteomic study of amyloid beta (25–35) peptide exposure to neuronal cells: Impact on APE1/Ref‐1's protein–protein interaction
Author(s) -
Mantha Anil K.,
Dhiman Monisha,
Taglialatela Giulio,
PerezPolo Regino J.,
Mitra Sankar
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23018
Subject(s) - biology , amyloid beta , microbiology and biotechnology , base excision repair , programmed cell death , dna damage , dna repair , dna (apurinic or apyrimidinic site) lyase , neurotoxicity , nuclear lamina , biochemistry , chemistry , nuclear protein , peptide , dna , apoptosis , gene , transcription factor , organic chemistry , toxicity
The genotoxic, extracellular accumulation of amyloid β (Aβ) protein and subsequent neuronal cell death are associated with Alzheimer's disease (AD). APE1/Ref‐1, the predominant apurinic/apyrimidinic (AP) endonuclease and essential in eukaryotic cells, plays a central role in the base excision repair (BER) pathway for repairing oxidized and alkylated bases and single‐strand breaks (SSBs) in DNA. APE1/Ref‐1 is also involved in the redox activation of several trans‐acting factors (TFs) in various cell types, but little is known about its role in neuronal functions. There is emerging evidence for APE1/Ref‐1's role in neuronal cells vulnerable in AD and other neurodegenerative disorders, as reflected in its nuclear accumulation in AD brains. An increase in APE1/Ref‐1 has been shown to enhance neuronal survival after oxidative stress. To address whether APE1/Ref‐1 level or its association with other proteins is responsible for this protective effect, we used 2‐D proteomic analyses and identified cytoskeleton elements (i.e., tropomodulin 3, tropomyosin alpha‐3 chain), enzymes involved in energy metabolism (i.e., pyruvate kinase M2, N‐acetyl transferase, sulfotransferase 1c), proteins involved in stress response (i.e., leucine‐rich and death domain, anti‐NGF30), and heterogeneous nuclear ribonucleoprotien‐H (hnRNP‐H) as being associated with APE1/Ref‐1 in Aβ(25–35)‐treated rat pheochromocytoma PC12 and human neuroblastoma SH‐SY5Y cell lines, two common neuronal precursor lines used in Aβ neurotoxicity studies. Because the levels of some of these proteins are affected in the brains of AD patients, our study suggests a neuroprotective role for APE1/Ref‐1 via its association with those proteins and modulating their cellular functions during Aβ‐mediated neurotoxicity. © 2012 Wiley Periodicals, Inc.