TY - JOUR
T1 - Resistance to the apoptotic effect of aggregated amyloid-β peptide in several different cell types including neuronal- and hepatoma-derived cell lines
AU - Mazziotti, Mark
AU - Perlmutter, David H.
PY - 1998/6/1
Y1 - 1998/6/1
N2 - There is a large body of literature indicating that aggregated amyloid-β peptide (Aβ) is toxic to neurons and suggesting that this neurotoxicity represents the final common pathway for neuronal degeneration in Alzheimer's disease. Previous studies have shown the outgrowth of a subclone of the rat neuronal cell line PC12 that is resistant to the toxic effect of aggregated Aβ peptide if the parent cell line is grown in the presence of aggregated Aβ peptide for a number of passages. To begin to characterize the mechanism by which PC12 cells become resistant to the apoptotic effect of Aβ peptide, in the present study we examined whether the resistance was specific to aggregated peptides, specific to an apoptotic form of cell death, and specific in cell type or was a general resistance to cell death that could be elicited in diverse cell types. The results show that the resistance is specific to compounds that have apoptotic effects through the generation of hydroxyl radical or H2O2, including aggregated Aβ-(25-35), Aβ-(1-40), Aβ-(1-42), Aβ-(1-43), amylin, 6-hydroxydopamine and H2O2 itself. The resistant subclones of PC12 were not resistant to other forms of apoptotic cell death or to necrotic cell death. The resistant state was also identified in a human hepatoma cell line, HepG2, when it was grown in the presence of aggregated Aβ-(25-35) for several passages, indicating that the mechanism(s) or molecule(s) responsible for this resistance are not restricted to neuronal cells and may be relevant to the pathobiology of oxidative injury in other cell types.
AB - There is a large body of literature indicating that aggregated amyloid-β peptide (Aβ) is toxic to neurons and suggesting that this neurotoxicity represents the final common pathway for neuronal degeneration in Alzheimer's disease. Previous studies have shown the outgrowth of a subclone of the rat neuronal cell line PC12 that is resistant to the toxic effect of aggregated Aβ peptide if the parent cell line is grown in the presence of aggregated Aβ peptide for a number of passages. To begin to characterize the mechanism by which PC12 cells become resistant to the apoptotic effect of Aβ peptide, in the present study we examined whether the resistance was specific to aggregated peptides, specific to an apoptotic form of cell death, and specific in cell type or was a general resistance to cell death that could be elicited in diverse cell types. The results show that the resistance is specific to compounds that have apoptotic effects through the generation of hydroxyl radical or H2O2, including aggregated Aβ-(25-35), Aβ-(1-40), Aβ-(1-42), Aβ-(1-43), amylin, 6-hydroxydopamine and H2O2 itself. The resistant subclones of PC12 were not resistant to other forms of apoptotic cell death or to necrotic cell death. The resistant state was also identified in a human hepatoma cell line, HepG2, when it was grown in the presence of aggregated Aβ-(25-35) for several passages, indicating that the mechanism(s) or molecule(s) responsible for this resistance are not restricted to neuronal cells and may be relevant to the pathobiology of oxidative injury in other cell types.
UR - http://www.scopus.com/inward/record.url?scp=0032104213&partnerID=8YFLogxK
U2 - 10.1042/bj3320517
DO - 10.1042/bj3320517
M3 - Article
C2 - 9601082
AN - SCOPUS:0032104213
VL - 332
SP - 517
EP - 524
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 2
ER -