Depolarization-induced polyadp-ribosylatlon of nuclear proteins in the brain-cortex stimulation-dependent regulation of dna transcription and repair in neuronal cells

The ability of neuronal cells to communicate and to respond to external signals appears to be critical for their survival We recently demonstrated polyADP-ribosylation of nuclear proteins in response to membrane depolarization in neurons prepared from rat brain-cortex This voltage-induced effect was attributed to a depolarization-induced activation of polyADP-ribose-polymerase (PARP), a nuclear protein in eukaryotes that catalyzes polyADP-ribosylation of proteins participating in DNA transcription, replication and repair, and thereby modulates their activity. Since PARP activation is accompanied by its auto-poly AD P-nbosylation, both in situ immunolabeling, of ADP-ribosepolymers in ihe cell nuclei and immunoprecipitation of the polyADP-ribosylated PARP may indicate PARP activation PolyADP-ribosylation of PARP and other nuclear proteins was observed in depolarized cortical neurons The activity of topoisomerase-1 in these neurons was modulated by membrane depolarization, concomitant with the activation of PARP, attributing modulation of topoisomerase-I activity to depolarization-induced activation of PARP On the basis of these recent findings, activation of PARP by membrane depolarization may suggest a stimulation-dependent regulatory mechanism, controlling DNA transcription and repair, which implies dependence of neuronal cells survival on their excitability.