Extracellular alpha-synuclein and its neurotoxic fragment NAC peptide induce cell death by different molecular pathways

• Autorzy: Kazimierczak A. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

Extracellular alpha-synuclein (ASN, NACP ñ NAC Precursor Protein) was suggested to play a crucial role in the pathogenesis of various neurodegenerative diseases such as Parkinsonís disease and Alzheimerís disease. The fragment corresponding to the region 61-95 of the protein, originally termed NAC (non-amyloidbeta component), has been found in amyloid plaques associated with Alzheimerís disease, and several reports suggest that this region is responsible for the toxicity of alpha-synuclein. However, the precise mechanism of ASN and NAC action remains unclear. The aim of the present study was to investigate the signaling events in ASN and NAC mediated apoptosis of neuronal PC12 cells. Immunochemical, spectrophotometrical and spectrofl uorometrical methods were used in this study. Our data evaluated by MTT assay and Hoechst 33342 showed that soluble ASN and NAC peptide, in concentration dependent manner, induce enhancement of free radicals level and apoptotic death of PC12 cells by 50% and 70%, respectively. ASN induced caspase-3 activation by 40% with concomitant decrease in poly(ADP-ribose) polymerase (PARP) immunoreactivity and had no effect on AIF release from mitochondria. On the contrary, NAC peptide had no effect on caspase-3 activity and PARP protein level, but enhanced PARP activity and induce AIF release. Inhibitor of caspase-3 (Z-DEVD-FMK, 100 microM) prevented large population of cells against ASN-evoked cell death, but had no signifi cant protective effect on cells treated with NAC peptide. These fi ndings indicate that ASN and its liberated neurotoxic fragment induce different signaling pathways of programmed cell death. Supported by the MS&HE Grant No 2PO5A4129 and MS&HE Scientifi c Network No 28/E-32/SN-0053/2007

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.84-85

Twórcy

autor

Kazimierczak A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland