title: Post-treatment with the Ca(2+)-Mg(2+)-endonuclease inhibitor aurintricarboxylic acid prevents peroxynitrite-induced DNA damage and death of murine astrocytes.
abstract: Oxidative stress plays critical roles in aging, cell death, and many diseases. Peroxynitrite is one of the major reactive oxygen species which mediates cell injury in a number of illnesses. It is of importance to identify the downstream events in peroxynitrite-initiated cell death cascade for preventing peroxynitrite toxicity. Ca(2+)-Mg(2+)-endonucleases have been suggested as the endonucleases that execute DNA fragmentation in several apoptotic cascades. In this study, we determined if astrocytes and neurons express the genes of Ca(2+)-Mg(2+)-endonucleases. We also tested our hypothesis that post-treatment with the Ca(2+)-Mg(2+)-endonuclease inhibitor aurintricarboxylic acid can decrease peroxynitrite-induced DNA damage and death of astrocytes. We found that both astrocytes and neurons express DNase I-like endonuclease-a major isoform of Ca(2+)-Mg(2+)-endonucleases. Treatment of astrocytes with aurintricarboxylic acid either before or after peroxynitrite exposures can profoundly decrease peroxynitrite-induced DNA damage and cell death. These results suggest that Ca(2+)-Mg(2+)-endonucleases may be a key downstream component in peroxynitrite-initiated cell death cascade in astrocytes and some other cell types, and aurintricarboxylic acid could be used to decrease peroxynitrite-induced DNA damage at delayed phases.
authors.affiliation: Department of Neurology, Veterans Affairs Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
authors.forename: Keqing
authors.initials: K
authors.lastname: Zhu
authors.forename: Huafei
authors.initials: H
authors.lastname: Lu
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D001312:Aurintricarboxylic Acid / Q000008:administration & dosage*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors*; D051379:Mice; D030421:Peroxynitrous Acid / Q000633:toxicity*
chemical_list: D030421:Peroxynitrous Acid; D001312:Aurintricarboxylic Acid; D004706:Endodeoxyribonucleases; C029367:calcium magnesium dependent endodeoxyribonuclease