Selective increase in cellular A beta 42 is related to apoptosis but not necrosis.
Amyloid beta protein ending at 42 (A beta 42) plays an important role in the pathology of Alzheimer's disease (AD). Here we show an increase in cellular A beta 42 in damaged neurons, with both ELISA and immunocytochemistry. The cellular A beta 42 increase was caused by 3-day treatments with H2O2, etoposide or melphalan, all of which induce genotoxic apoptosis, but not by treatment with sodium azide, which causes necrosis. Secreted A beta was similarly decreased with all these treatments. The cellular A beta 42 increase appeared even with minimal damage (ELISA) and A beta 42-positive cells were TUNEL negative (double staining), indicating that any early apoptosis mechanism may induce the cellular A beta 42 increase. Thus, neuronal apoptosis and cellular A beta 42 increase may be linked in a way that contributes importantly to AD pathology.
Ohyagi
Y
Y
Department of Pharmacology, Mayo Clinic Jacksonville, FL 32224, USA.
Yamada
T
T
Nishioka
K
K
Clarke
N J
NJ
Tomlinson
A J
AJ
Naylor
S
S
Nakabeppu
Y
Y
Kira
J
J
Younkin
S G
SG
D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005047:Etoposide / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008558:Melphalan / Q000494:pharmacology; D009336:Necrosis; D010446:Peptide Fragments / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019810:Sodium Azide / Q000633:toxicity
D016229:Amyloid beta-Peptides; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D005047:Etoposide; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D008558:Melphalan