作者
Yingfei Wang, Ran An, George K Umanah, Hyejin Park, Kalyani Nambiar, Stephen M Eacker, BongWoo Kim, Lei Bao, Maged M Harraz, Calvin Chang, Rong Chen, Jennifer E Wang, Tae-In Kam, Jun Seop Jeong, Zhi Xie, Stewart Neifert, Jiang Qian, Shaida A Andrabi, Seth Blackshaw, Heng Zhu, Hongjun Song, Guo-li Ming, Valina L Dawson, Ted M Dawson
发表日期
2016/10/7
期刊
Science
卷号
354
期号
6308
页码范围
aad6872
出版商
American Association for the Advancement of Science
简介
INTRODUCTION
Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) is a nuclear enzyme responding to oxidative stress and DNA damage. Excessive activation of PARP-1 causes an intrinsic caspase-independent cell death program designated parthanatos, which occurs in many organ systems because of toxic or stressful insults, including ischemia-reperfusion injury after stroke and myocardial infarction, inflammatory injury, reactive oxygen species–induced injury, glutamate excitotoxicity, and neurodegenerative diseases. Inhibition or genetic deletion of PARP-1 is profoundly protective against such cellular injury in models of human disease.
RATIONALE
The molecular mechanisms underlying parthanatos involve release of mitochondrial apoptosis-inducing factor (AIF) and its translocation to the nucleus, which results in chromatinolysis into 20- to 50-kb large DNA fragments—a commitment point for parthanatos …
学术搜索中的文章
Y Wang, R An, GK Umanah, H Park, K Nambiar… - Science, 2016