Title: Functional mitochondria are required for amyloid beta-mediated neurotoxicity
Authors: Cardoso, Sandra Morais 
Santos, Sancha 
Swerdlow, Russell H. 
Oliveira, Catarina R. 
Keywords: Alzheimer's disease;Mitochondria;β-amyloid;ρ0 cells
Issue Date: Jun-2001
Publisher: The Federation of American Societies for Experimental Biology
Citation: The FASEB Journal. 15:8 (2001) 1439-1441
Abstract: The role of mitochondria in amyloid bpeptide (Ab)-induced cytotoxicity is unclear. We therefore exposed NT2 cells, a clonal human teratocarcinoma cell line capable of differentiation into terminal neurons, to Ab 25-35 or to Ab 1-42 to evaluate cell viability and altered mitochondrial function. A 24-h incubation of native NT2 cells (r+ cells) with Ab 25-35 or with Ab 1-42 produced a dose-dependent decline in MTT reduction. Ab 1-42 was shown to be more toxic compared with Ab 25-35. Ab 25-35 toxicity was prevented or diminished by a 22-h preincubation with antioxidants (vitamin E, melatonin, and idebenone), as well as by simultaneous incubation with GSH or the nicotinic receptor agonist nicotine. Ab 25-35 exposure was also associated with (1) inhibition of mitochondrial respiratory chain complexes (I, NADH-ubiquinone oxidoreductase; II/III, succinate-cytochrome c oxidoreductase; and IV, cytochrome c oxidase), (2) ATP depletion, and (3) reduction of the mitochondrial membrane potential. In contrast, NT2 cells rendered incapable of oxidative phosphorylation via depletion of their mitochondrial DNA (r0 cells) were unaffected by exposure to Ab 25-35 or Ab 1-42. These data indicate that Ab can disrupt mitochondrial function and that such disruption causes oxidative stress. It is further suggested that a functional mitochondrial respiratory chain is required for Ab toxicity
URI: http://hdl.handle.net/10316/12830
ISSN: 0892-6638
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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