Arsenic exposure inhibits poly (ADP)-ribosylation of nuclear proteins in PC-12 cells and rat brain Chapter uri icon


  • Context: Recent reports demonstrate that poly (ADP)-ribosylation participates in learning processes, together with other epigenetic mechanisms of chromatin remodeling. The enzyme poly (ADP-ribose) polymerase 1 (PARP-1) has zinc finger domains that are target of inhibition by arsenic, therefore inhibition of this enzyme in the central nervous system may contribute to the cognitive deficits observed in humans after prolonged low level arsenic exposure, especially during development. Objective: The aim of this work was to evaluate in vitro and in vivo PARP-1 inhibition by arsenite. Materials and methods: PARP-1 activity was analyzed by quantification of substrate concentration (NAD%2b) and immunoreactivity for the reaction products (poly (ADP-ribosylated) proteins) in arsenic exposed PC-12 cells (0.1 and 1 uM). The same endpoints were evaluated in the brain of life-long arsenic exposed rats, from gestation through lactation until adult age (3 ppm, drinking water). Results: PARP-1 inhibition was demonstrated through decreased immunoreactivity to PAR polymers and increased concentrations of PARP-1 substrate NAD%2b in PC12 cells and in regions of the rat brain involved in learning and memory. Also, exposed animals showed poor performance in an associative memory test. Discussion and conclusion: The demonstrated PARP-1 inhibition in the nervous system of arsenic exposed rats and in PC-12 cells may be related to arsenic-induced cognitive deficits. Besides alterations of DNA methylation, this inhibition is another epigenetic modification associated with exposure to a neurotoxicant. © 2014 by Nova Science Publishers, Inc. All rights reserved.

publication date

  • 2014-01-01