Selective Down-Regulation of Nuclear Poly(ADP-Ribose) Glycohydrolase

作者: David M. Burns , Weihai Ying , Tiina M. Kauppinen , Keqing Zhu , Raymond A. Swanson

DOI: 10.1371/JOURNAL.PONE.0004896

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摘要: Author(s): Burns, David M; Ying, Weihai; Kauppinen, Tiina Zhu, Keqing; Swanson, Raymond A | Abstract: BackgroundThe formation of ADP-ribose polymers on target proteins by poly(ADP-ribose) polymerases serves a variety cell signaling functions. In addition, extensive activation polymerase-1 (PARP-1) is dominant cause death in ischemia-reperfusion, trauma, and other conditions. Poly(ADP-ribose) glycohydrolase (PARG) degrades the formed acceptor PARP-1 PARP family members. PARG exists as multiple isoforms with differing subcellular localizations, but functional significance these uncertain.Methods / principal findingsPrimary mouse astrocytes were treated an antisense phosphorodiamidate morpholino oligonucleotide (PMO) targeted to exon 1 full-length suppress expression this nuclear-specific isoform. The antisense-treated cells showed down-regulation both nuclear immunoreactivity enzymatic activity, without significant alteration cytoplasmic activity. When genotoxic agent MNNG induced activation, delayed rate PAR degradation, reduced condensation, death.Conclusions/significanceThese results support preferentially localization for PARG, suggest key role isoform pathway.

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