Auto-Modification of Poly (ADP-Ribose) Polymerase and Membrane Lipid Composition as Diagnostic Tools to Measure the Physio-Pathological State of the Cell

Abstract

Poly(ADPribosyl)ation, catalysed by poly(ADP-ribose)polymerases, affects many cellular events and has a recognized epigenetic role. Nuclear poly(ADP-ribose)polymerases 1 and 2 are hyper activated by DNA strandbreaks. They auto-modify with large polymers of ADP-ribose and recruit DNA repair proteins. The more the DNA strand-breaks, the more poly(ADP-ribose) polymerase modifies itself.On the other hand, dietary lipids can be signaling molecules, lead to pro-(ω6)/ anti-(ω3) inflammatory compounds, and be included in biomembranes, good biomarkers of their unbalance.Here, we report the results obtained from an epidemiological study to establish whether the combination of two different analyses, i.e. detecting auto-modified poly (ADP-ribose) polymerase levels and analyzing erythrocyte membrane fatty acid composition, might help to monitor the physio-pathological state of the cell, and to correlate with lifestyle, diet or diseases. The two analyses were carried blindly on 70 subjects undergoing endoscopy. They were first interviewed, to collect anamnesis and clinical data, if present. Lymphocytes and erythrocytes were prepared from venous blood to assay poly (ADP-ribose) polymerase auto modification and membrane fatty acid content, respectively. The results were statistically evaluated. The measure of poly (ADP-ribose) polymerase automodification confirmed that its levels correlate with DNA damage extent, within the same pathology, and allowed to monitor the clinical activity of the disease, depending on ongoing therapeutic/surgical treatment. Membrane fat profile was able to evidence unbalance of lipids linked to both diet/lifestyle and inflammatory states leading to diseases. Both analyses provide possible biomarkers for sensible, non-invasive and routine monitoring.