Gene expression profiles for mitochondria sirtuins and poly(ADP-ribose) polymerases in amyloid Beta toxicity

• Autorzy: Strosznajder R. , Wencel P.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Sirtuins (SIRTs) and poly(ADPribose) polymerases (PARPs) are NAD dependent enzymes engaged in the regulation of energy metabolism, transcription, DNA replication and repair. SIRTs type III histone deacetylases (HDAC) target histone and many other proteins in nucleus, cytoplasm and mitochondria. PARP-1 is responsible for over 90% of poly (ADPribosylation) in the brain. However, the role of these NAD dependent enzymes in neurodegeneration /neuroprotection is till now not fully elucidated. In many neurodegenerative disorders metabolism of amyloid precursor protein (APP) is altered, amyloid beta (Aβ) is released and NAD dependent metabolic pathways are affected. This study focused on gene expression profiles for SIRTs and PARPs and on their functional relationship in cells survival/death under Aβ toxicity. METHODS: PC-12 cells after exposition on exogenous Aβ1-42 oligomers (ABO -1 mM, 24 h) were used. Moreover, the effect of endogenously liberated Aβ in PC12 cells transfected with human gene for APP wild type (APPwt) and bearing Swedish mutation (APPsw) was investigated. The both served as experimental models. RESULTS: Our data indicated that ABO suppressed alpha secretase and enhanced gene expression for beta and gamma secretases. Moreover, ABO upregulated the gene expression for PARP-1, PARP-2 and SIRT4 which is responsible for monoADPribosylation of several mitochondrial proteins. The endogenously liberated Aβ in APPwt cells upregulated gene expression for PARP-1, -2 and decreased for SIRT5. In APPsw cells activation of genes for PARP -1,-2,-9 and for SIRT3 was observed. In our previous study we observed significant suppression of PARP activity in APPsw cells. CONCLUSIONS: These results suggest that NAD is not used by PARPs in APPsw cells and it may be available for Sirt3 which is involved in regulation of antioxidative enzymes. The functional interactions between these NAD dependent enzymes may play crucial role in regulation of cell survival under Aβ peptide toxicity. Supported by MRC.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S35-S36

Twórcy

autor

Strosznajder R.

• Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Wencel P.

• Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland