Non-Abeta component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria

• Autorzy: Adamczyk A. , Czapski G.A. , Jesko H. , Strosznajder R.P.
• Języki publikacji: EN

Abstrakty

EN

Amyloid beta peptide (Aß) and non-Aß component of Alzheimer’s disease amyloid (NAC) are involved in pathomechanism of Alzheimer's Disease (AD) and are deposited in the AD brain in the form of senile plaques. However, the mechanism of their neurotoxicity is not fully understood. In this study the sequence of events involved in NAC and Aß peptides evoked toxicity was investigated in brain slices, synaptosomes and in subcellular fractions. Radio-, immunochemical, spectrophotometrical methods and DNA electrophoresis were used in this study. Our data indicated that Aß 1-40 (25 µM) and NAC (10 µM) peptides induced liberation of free radicals and massive DNA damage that lead to activation of DNA bound enzyme poly(ADP-ribose) polymerase-1 (PARP-1). In consequence of these processes apoptosis-inducing factor (AIF) was released from mitochondria and was translocated to nucleus. The inhibitor of PARP, 3-aminobenzamide significantly decreased AIF release from mitochondria and its translocation. Both peptides under the investigated conditions had no effect on caspase-3 activity. Our data indicated that Aß and NAC peptides stimulate AIF-dependent apoptotic pathway that seems to be caspase independent process. The inhibition of PARP-1 may protect the brain against Aß and NAC toxicity.

Słowa kluczowe

EN

Alzheimer's disease; amyloid beta peptide; apoptosis-inducing factor; DNA degradation; reactive oxygen species; senile plaque; poly[ADP-ribose] polymerase-1; rat; neurotoxicity; brain mitochondrion

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology. Supplement
• Rocznik: 2005
• Tom: 56
• Numer: 2
• Opis fizyczny: p.5-13.,fig.,ref.

Twórcy

autor

Adamczyk A.

• Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland

autor

Czapski G.A.

autor

Jesko H.

autor

Strosznajder R.P.