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Collegium antropologicum, Vol.32 - Supplement 1 No.1 Svibanj 2008.

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Mitochondria Morphology and DNA Content upon Sublethal Exposure to Beta-Amyloid1–42 Peptide

Andrea Diana
Goran Šimić
Elena Sinforiani
Nicola Orrù
Giuseppina Pichir
Giorgio Bono

Puni tekst: engleski, pdf (174 KB) str. 51-58 preuzimanja: 347* citiraj
Diana, A., Šimić, G., Sinforiani, E., Orrù, N., Pichir, G., Bono, G. (2008). Mitochondria Morphology and DNA Content upon Sublethal Exposure to Beta-Amyloid1–42 Peptide. Collegium antropologicum, 32 - Supplement 1(1), 51-58. Preuzeto s

Brains affected by Alzheimer’s disease (AD) show a large spectrum of mitochondrial alterations at both morphological
and genetic level. The causal link between amyloid beta peptides (Ab) and mitochondrial dysfunction has been established
in cellular models of AD using Ab concentrations capable of triggering massive neuronal death. However, mitochondrial
changes related to sublethal exposure to Ab are less known. Here we show that subtoxic, 1 mMAb1–42 exposure
does not change the mitochondrial shape of living cells, as visualized upon the uptake of the non-potentiometric fluorescent
probe Mitotracker Green and enhanced yellow fluorescent protein (EYFP)-tagged cytochrome c oxidase expression.
Immunolocalization of oxidative adducts 8-hydroxy-2’-deoxyguanosine, 8-hydroxyguanine and 8-hydroxyguanosine demonstrates
that one-micromolar concentration of Ab1–42 is also not sufficient to elicit dramatic qualitative changes in the
RNA/DNA oxidative products. However, in comparison with controls, semi-quantitative analysis of the overall mitochondrial
mass by integrated fluorescence intensity reveals an ongoing down-regulation in mitochondrial biosynthesis or,
conversely, an enhanced autophagic demise of Ab treated cells. Furthermore, a significant increase of the full-length mitochondrial
DNA (mtDNA) from Ab-treated versus control cells is found, as measured by long range polymerase chain
reaction (PCR). Such up-regulation is accompanied by extensive fragmentation of the unamplified mtDNA, probably due
to the detrimental effect of Ab. We interpret these results as a sequence of compensatory responses induced by mtDNA
damage, which are devoted to repression of oxidative burst. In conclusion, our findings suggest that early therapeutic interventions
aimed at prevention of mitochondrial oxidative damage may delay AD progression and help in treating AD

Ključne riječi
amyloid toxicity; mitochondrial DNA; neuroblastoma cell culture; oxidative stress

Hrčak ID: 24553


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