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| Content Provider | Springer Nature Link |
|---|---|
| Author | Zhang, Yuanyuan Yang, Yang Xie, Zhen Zuo, Wenqi Jiang, Hongyan Zhao, Xueyan Sun, Yu Kong, Weijia |
| Copyright Year | 2015 |
| Abstract | Oxidative damage to the inner ear is responsible for several types of sensorineural deafness. Cochlear stria marginal cells (MCs) are thought to be vulnerable to such oxidative stress. Activated poly(ADP-ribose) polymerase 1 (PARP1) has been implicated in several diseases, but the effect of PARP1 on MCs subjected to oxidative stress remains elusive. In this study, we established an in vitro cellular oxidative stress model using glucose oxidase (GO) and attempted to explore the role that PARP1 plays in the oxidative damage of MCs. In this study, PARP1 and poly-ADP-ribose (PAR) were highly expressed in GO-treated MCs, and this was accompanied by loss of MC viability, excessive generation of reactive oxygen species (ROS), collapse of mitochondria membrane potential (ΔΨm), and redistribution of the mitochondrial downstream pathway-related molecules Bax and cytochrome c, eventually causing MC death. These effects were almost completely counteracted by suppressing PARP1 expression with small interfering RNA (siRNA). We also found that caspase-3 activation was a downstream event of PARP activation and that apoptosis of MCs was suppressed, although not completely, by pretreatment with the pan-caspase inhibitor z-VAD-fmk. The suppression was less than that when PARP1 expression was inhibited. We conclude that GO treatment induces activation of PARP1, which causes MC damage via mitochondrial mediation. PARP1 plays a pivotal role in GO-induced MC death, at least in part, via the caspase-3 cascade. Our study might provide a new cellular and molecular approach for the treatment of oxidative stress-related sensorineural deafness. |
| Starting Page | 5971 |
| Ending Page | 5984 |
| Page Count | 14 |
| File Format | |
| ISSN | 08937648 |
| Journal | Molecular Neurobiology |
| Volume Number | 53 |
| Issue Number | 9 |
| e-ISSN | 15591182 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-11-02 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Poly(ADP-ribose) polymerase 1 Marginal cell Hearing loss Oxidative stress Mitochondria Apoptosis Neurosciences Neurobiology Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cellular and Molecular Neuroscience |
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