Posttreatment with the Ca2+-Mg2+-dependent endonuclease inhibitor aurintricarboxylic acid abolishes genotoxic agent-induced nuclear condensation and DNA fragmentation and decreases death of astrocytes
✍ Scribed by Huafei Lu; Gangwei Wei; Dongmin Wang; Patrick Yung; Weihai Ying
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 220 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
DNA fragmentation and nuclear condensation are important nuclear changes in apoptosis. In this study we determined whether DNA fragmentation and nuclear condensation occur in astrocytes treated with 100–200 μM of the genotoxic agent M‐nitroso‐N‐nitroguanidine (MNNG). Our study also investigated the roles of Ca^2+^‐Mg^2+^‐dependent endonuclease (CME) in the MNNG‐induced nuclear changes. We found that MNNG induced profound ATP depletion as well as marked nuclear condensation and DNA fragmentation in the cells. Both the nuclear condensation and the DNA fragmentation were abolished by posttreatment of the cells with the CME inhibitor aurintricarboxylic acid (ATA). The ATA posttreatment also significantly, but only partially, decreased MNNG‐induced cell death. In contrast, pretreatment plus cotreatment with ATA did not affect either MNNG‐induced nuclear condensation or cell death. Our study further suggests that ATA does not decrease the cytotoxicity of MNNG by directly inhibiting poly(ADP‐ribose) polymerases. Collectively, our observations suggest that MNNG can induce both DNA fragmentation and nuclear condensation in astrocytes by a CME‐dependent mechanism, which partially contributes to the genotoxic agent‐induced cell death. Published 2008 Wiley‐Liss, Inc.