beta-amyloid induces caspase-dependent early neurotoxic change in PC12 cells: correlation with H2O2 neurotoxicity.
We examined neurotoxic effects of Abeta(25-35), an active fragment of beta-amyloid (Abeta), and compared the effect with H2O2 neurotoxicity in PC12 cells. Abeta(25-35) induced the loss of mitochondria function as detected using a tetrazolium salt (WST-1) reduction assay and decreased the number of cells adhering to collagen type 1-coated plates. Abeta(25-35) did not induce cell death, as detected by Hoechst 33342/propidium iodide staining. The caspase tetrapeptide inhibitor z-IETD-fluoromethylketone (FMK) and z-LEHD-FMK inhibited the attenuation of WST-1 reduction induced by Abeta(25-35) and H2O2, while the caspase-3 inhibitor z-DEVD-FMK afforded protection only against H2O2 neurotoxicity. Caspase-3 protease activity was increased by treatment of H2O2 but not Abeta(25-35). Thus, Abeta(25-35) induces early neurotoxic events by activating caspases other than caspase-3. H2O2 -induced oxidative stress may not be implicated in Abeta-induced neurotoxic pathways.
Saito
T
T
Pharmacology Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Company, Limited, 1-403 Yoshino-cho, Omiya, 330-8530, Saitama, Japan. s17134@ccm.taisho.co.jp
Kijima
H
H
Kiuchi
Y
Y
Isobe
Y
Y
Fukushima
K
K
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D016229:Amyloid beta-Peptides; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009498:Neurotoxins; D009842:Oligopeptides; D010446:Peptide Fragments; D013778:Tetrazolium Salts; C113041:amyloid beta-protein (35-25); C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases