Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death.
Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death.
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DOI：
10.1007/s00018-010-0533-1
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发表时间：
2011-04
影响因子：
8
通讯作者：
Althaus, Felix R.
中科院分区：
文献类型：
--
作者：
Blenn, C.;Wyrsch, P.;Bader, J.;Bollhalder, M.;Althaus, Felix R.
对细胞的氧化性DNA损伤激活聚（ADP-核糖）聚合酶-1（PARP-1），并且所形成的聚（ADP-核糖）被聚（ADP-核糖）糖水解酶（PARG）快速降解为ADP-核糖。在这里，我们表明，PARP-1和PARG控制细胞外Ca2+通量通过melastatin样瞬时受体电位2通道（TRPM2）在细胞死亡信号通路。TRPM2激活基本上导致整个Ca2+流入胞质溶胶，激活半胱天冬酶并导致凋亡诱导因子（AIF）从线粒体内膜易位至细胞核，随后细胞死亡。PARP-1或PARG功能的消除破坏了这些信号并减少了细胞死亡。细胞的ADP-核糖负载在不存在氧化损伤的情况下诱导Ca2+通量，表明ADP-核糖是调节TRPM2的PARP-1/PARG系统的关键代谢物。我们得出结论，PARP-1/PARG控制细胞死亡信号通路，该通路在五个不同的细胞隔室之间运作，并通过三种类型的化学信使进行通信：核苷酸，阳离子和蛋白质。本文的在线版本（doi：10.1007/s00018 - 010 - 0533 - 1）包含补充材料，可供授权用户使用。
Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca2+ fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca2+ influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca2+ fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and proteins. The online version of this article (doi:10.1007/s00018-010-0533-1) contains supplementary material, which is available to authorized users.
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影响因子：
7.3
作者：
Fonfria, E;Marshall, ICB;McNulty, S
通讯作者：
McNulty, S
DOI：
10.1016/j.jchromb.2005.05.002
发表时间：
2005-07-25
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影响因子：
7.8
作者：
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