PMID- 19656264 OWN - NLM STAT- MEDLINE DCOM- 20091009 LR - 20181201 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 111 IP - 1 DP - 2009 Oct TI - Poly(ADP-ribose) polymerase-1 modulation of in vivo response of brain hypoxia-inducible factor-1 to hypoxia/reoxygenation is mediated by nitric oxide and factor inhibiting HIF. PG - 150-9 LID - 10.1111/j.1471-4159.2009.06307.x [doi] AB - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that once activated by genotoxic agents, modulates its own activity and that of several other nuclear proteins. The absence or pharmacological inhibition of this protein has been proven to be beneficial in the treatment of different diseases involving a hypoxic situation. We previously reported that PARP-1 modulates the hypoxia-inducible factor-1 (HIF-1) response in vitro, but this effect has not yet been demonstrated in vivo. The brain is especially susceptible to hypoxic injury, and the present study demonstrates that PARP-1 plays a major role in the post-hypoxic response of HIF-1alpha in the cerebral cortex. Immediate post-hypoxic HIF-1alpha accumulation was higher in the presence of PARP-1, and this differential response was mediated by nitric oxide and to a lesser extent, reactive oxygen species. PARP-1 was also found to induce a more rapid but less sustained HIF-1 transcriptional activity by up-regulating the factor inhibiting HIF. The implication of PARP-1 in these results was further demonstrated by pharmacologically inhibiting PARP in wild-type mice. In conclusion, our data suggest that PARP-1 has an important regulatory role in the in vivo response of brain HIF-1 to hypoxia/reoxygenation. FAU - Martinez-Romero, Ruben AU - Martinez-Romero R AD - Department of Experimental Biology. University of Jaen Paraje Las Lagunillas s/n, Jaen, Spain. FAU - Canuelo, Ana AU - Canuelo A FAU - Martinez-Lara, Esther AU - Martinez-Lara E FAU - Javier Oliver, Francisco AU - Javier Oliver F FAU - Cardenas, Sara AU - Cardenas S FAU - Siles, Eva AU - Siles E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090727 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Enzyme Inhibitors) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Free Radical Scavengers) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Isoquinolines) RN - 0 (Piperidines) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 31C4KY9ESH (Nitric Oxide) RN - 5007H57E2L (3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone) RN - EC 2.4.2.30 (Parp1 protein, mouse) RN - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - S798V6YJRP (Edaravone) RN - S88TT14065 (Oxygen) RN - T3CHA1B51H (Antipyrine) SB - IM MH - Analysis of Variance MH - Animals MH - Antipyrine/analogs & derivatives/pharmacology MH - Brain/drug effects/*metabolism MH - Disease Models, Animal MH - Edaravone MH - Enzyme Inhibitors/pharmacology MH - Excitatory Amino Acid Transporter 2/metabolism MH - Free Radical Scavengers/pharmacology MH - Gene Expression Regulation/drug effects/*physiology MH - *Hypoxia/metabolism/pathology/therapy MH - Hypoxia-Inducible Factor 1/*metabolism MH - Isoquinolines/pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nitric Oxide/*metabolism MH - Oxidative Stress/drug effects/physiology MH - Oxygen/*pharmacology/therapeutic use MH - Piperidines/pharmacology MH - Poly (ADP-Ribose) Polymerase-1 MH - Poly(ADP-ribose) Polymerase Inhibitors MH - Poly(ADP-ribose) Polymerases/deficiency/*physiology MH - RNA, Messenger/metabolism MH - Thiobarbituric Acid Reactive Substances/metabolism EDAT- 2009/08/07 09:00 MHDA- 2009/10/10 06:00 CRDT- 2009/08/07 09:00 PHST- 2009/08/07 09:00 [entrez] PHST- 2009/08/07 09:00 [pubmed] PHST- 2009/10/10 06:00 [medline] AID - JNC6307 [pii] AID - 10.1111/j.1471-4159.2009.06307.x [doi] PST - ppublish SO - J Neurochem. 2009 Oct;111(1):150-9. doi: 10.1111/j.1471-4159.2009.06307.x. Epub 2009 Jul 27.