Naslov
Mitochondria morphology and DNA content upon sublethal exposure to beta-amyloid 1-42 peptide

Autori
Diana, Andrea ; Šimić, Goran ; Sinforiani, Elena ; Orrù , Nicola ; Pichiri, Giuseppina ; Bono, Giorgio

Izvornik
Collegium Antropologicum (0350-6134) 32 (2008), S1; 51-58

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
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 (A beta) and mitochondrial dysfunction has been established in cellular models of AD using A beta concentrations capable of triggering massive neuronal death. However, mitochondrial changes related to sublethal exposure to A beta are less known. Here we show that subtoxic, 1 micromolar A beta(1-42) 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 A beta(1-42) 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 A beta treated cells. Furthermore, a significant increase of the full-length mitochondrial DNA (mtDNA) from A beta-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 A beta. 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 patients.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija

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