Disrupted ADP-ribose metabolism with nuclear Poly (ADP-ribose) accumulation leads to different cell death pathways in presence of hydrogen peroxide in procyclic Trypanosoma brucei

Parasites & Vectors
Mariana SchlesingerSilvia H Fernández Villamil

Abstract

Poly(ADP-ribose) (PAR) metabolism participates in several biological processes such as DNA damage signaling and repair, which is a thoroughly studied function. PAR is synthesized by Poly(ADP-ribose) polymerase (PARP) and hydrolyzed by Poly(ADP-ribose) glycohydrolase (PARG). In contrast to human and other higher eukaryotes, Trypanosoma brucei contains only one PARP and PARG. Up to date, the function of these enzymes has remained elusive in this parasite. The aim of this work is to unravel the role that PAR plays in genotoxic stress response. The optimal conditions for the activity of purified recombinant TbPARP were determined by using a fluorometric activity assay followed by screening of PARP inhibitors. Sensitivity to a genotoxic agent, H2O2, was assessed by counting motile parasites over the total number in a Neubauer chamber, in presence of a potent PARP inhibitor as well as in procyclic transgenic lines which either down-regulate PARP or PARG, or over-express PARP. Triplicates were carried out for each condition tested and data significance was assessed with two-way Anova followed by Bonferroni test. Finally, PAR influence was studied in cell death pathways by flow cytometry. Abolition of a functional PARP either by using ...Continue Reading

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Citations

Dec 21, 2018·Microbiology and Molecular Biology Reviews : MMBR·Pamlea N BradyMargaret A Johnson
Jul 22, 2019·Biochemical Pharmacology·Lichao ChenMitsuko Masutani

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Methods Mentioned

BETA
size exclusion chromatography
FCS
Dot blot
Fluorescence
transgenic
flow cytometry

Software Mentioned

Modeller
COOT
ImageJ
GraphPad Prism5
ClustalW
GraphPad Prism
Aline

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