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. 2014 Mar 26;8:47. doi: 10.3389/fnins.2014.00047

Figure 2.

Figure 2

Transcriptional activation of pro-inflammatory signaling in tandem with PARP-1 overactivation. Perinatal asphyxia decreases oxygen saturation in blood, leading to a switch from aerobic to a less efficient anaerobic metabolism involving lactate accumulation, acidosis and cell death. Re-oxygenation is essential for survival. Nevertheless, re-oxygenation induces oxidative stress, damaging several biomolecules including DNA. In response to DNA damage, PARP-1 increases its activity, recruiting the DNA repair machine. PARP-1 overactivation modifies several target proteins via poly (ADP-ribose) polymers (pADPr). One of the targets of pADPr ribosylation is NF-κB, whose p65 subunit is translocated to the nucleus, activating the transcription of pro-inflammatory (e.g., TNF-α, IL-1β, and IL-6), but also anti-inflammatory (e.g., IL-4, IL-10; IL-13) cytokines. The balance between pro- and anti-inflammatory cytokines is crucial for determining cell survival or death.