Expression of poly(ADP-ribose) polymerases in hippocampus during systemic inflammatory response. The role of PARP-1 protein interactions in cognition

• Autorzy: Czapski G. , Adamczyk A. , Strosznajder R.P. , Strosznajder J.B.
• Języki publikacji: EN

Abstrakty

EN

Poly(ADP-ribosyl)ation is covalent modification of proteins responsible for the alterations of their function. This process is catalyzed by poly(ADP-ribose)polymerases (PARP) family, consisted of 18 isoforms. Among target proteins, there are many DNA-related proteins and PARP-1 itself. In the brain, PARP-1 is responsible for more than 90% of poly(ADP-ribosyl)ation. PARP-1 plays a significant role in regulation of several transcription factors including NF-kB and p53. Our previous data indicated an important impact of PARP-1 in brain ischemia and in systemic inflammatory response (SIR). In this study we have analyzed the expression of PARP family genes in hippocampus of mice subjected to lipopolysaccharide (LPS)- evoked SIR. Moreover, the effect of SIR on PARP-1/PAR protein interaction and on memory function was evaluated. Mice C57BL6 were injected i.p. with LPS (1 mg/kg b.w.) alone or together with PARP inhibitors 3-aminobenzamide (30 mg/kg b.w.). The studies were carried out by using immunochemistry, microarray, real-time RT-PCR, and behavioral analysis. Our data indicated the small effect of SIR on PARP-1 gene expression level, however, expression of genes for PARP-3, -9, -12 and -14 was significantly increased 12 h after LPS administration. The level of PAR in hippocampus was elevated during SIR indicating activation of protein poly(ADP-ribosyl)ation. Moreover, further analysis of LPS-affected genes indicated that among 83 proteins known for their direct interaction with PARP-1, genes for 21 are present in SIR-related interactome, along with several genes for transcription factors and proteins involved in signal transduction. The enhancement of gene expression in hippocampus for several members of PARP family during SIR may be responsible for the alteration of PARPs function, higher level of PAR formation and for the modification of PARP/PAR protein interaction, transcription, cell signaling and memory. Our data indicated that SIR significantly decreases object recognition but has small effect on spatial memory. PARP-1 inhibitor protects against SIR induced molecular alteration in hippocampus and against SIR-evoked cognition impairment. Moreover, PARP-1 inhibitors significantly enhanced spatial memory in LPS treated mice. Our results indicate that inhibition of PARP-1 is a promising protective strategy during overactivation of inflammatory reaction. The role of other PARP family members in SIR is a target of our future investigation.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.145

Twórcy

autor

Czapski G.

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

autor

Adamczyk A.

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

autor

Strosznajder R.P.

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

autor

Strosznajder J.B.

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