Selective role for superoxide in InsP3 receptor-mediated mitochondrial dysfunction and endothelial apoptosis.
Selective role for superoxide in InsP3 receptor-mediated mitochondrial dysfunction and endothelial apoptosis.
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DOI：
10.1083/jcb.200505022
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发表时间：
2005-09-26
期刊：
影响因子：
--
通讯作者：
Fisher AB
中科院分区：
文献类型：
--
作者：
Madesh M;Hawkins BJ;Milovanova T;Bhanumathy CD;Joseph SK;Ramachandrarao SP;Sharma K;Kurosaki T;Fisher AB
在缺血/再灌注（I/R）损伤和相关炎症过程中，活性氧（ROS）在细胞存活和细胞死亡中起着不同的作用。在这项研究中，活性氧的产生激活的巨噬细胞诱发的细胞内钙（[Ca 2 +]i）瞬态的内皮细胞，被消融的超氧化物歧化酶和阴离子通道阻滞剂的组合。[Ca2[Ca 2 +]i库耗竭，而不是细胞外Ca 2+螯合，阻止[Ca 2 +]i升高响应O2 . -，这是肌醇1，4，5-三磷酸（InsP 3）依赖性，和细胞缺乏三个InsP 3受体（InsP 3R）亚型未能显示[Ca 2 +]i瞬变。重要的是，O2 .−触发的Ca 2+动员先于线粒体膜电位的损失，这与其他氧化剂和细胞衍生的ROS无关。细胞凋亡的激活选择性地发生在响应O2 .−，并可以防止[Ca 2 +]i缓冲。这项研究提供的证据表明，O2 .−促进了InsP 3R相关的凋亡级联反应，并可能在I/R损伤和炎症中发挥关键作用。
Reactive oxygen species (ROS) play a divergent role in both cell survival and cell death during ischemia/reperfusion (I/R) injury and associated inflammation. In this study, ROS generation by activated macrophages evoked an intracellular Ca2+ ([Ca2+]i) transient in endothelial cells that was ablated by a combination of superoxide dismutase and an anion channel blocker. [Ca2+]i store depletion, but not extracellular Ca2+ chelation, prevented [Ca2+]i elevation in response to O2 .− that was inositol 1,4,5-trisphosphate (InsP3) dependent, and cells lacking the three InsP3 receptor (InsP3R) isoforms failed to display the [Ca2+]i transient. Importantly, the O2 .−-triggered Ca2+ mobilization preceded a loss in mitochondrial membrane potential that was independent of other oxidants and mitochondrially derived ROS. Activation of apoptosis occurred selectively in response to O2 .− and could be prevented by [Ca2+]i buffering. This study provides evidence that O2 .− facilitates an InsP3R-linked apoptotic cascade and may serve a critical function in I/R injury and inflammation.
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影响因子：
3
作者：
Bernardi, P;Petronilli, V
通讯作者：
Petronilli, V
DOI：
10.1073/pnas.152571899
发表时间：
2002-07-23
影响因子：
11.1
作者：
Li, C;Fox, CJ;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
4.8
作者：
Assefa, Z;Bultynck, G;De Smedt, H
通讯作者：
De Smedt, H
DOI：
10.1083/jcb.145.4.795
发表时间：
1999-05-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Boitier E;Rea R;Duchen MR
通讯作者：
Duchen MR
影响因子：
3.5
作者：
Kikuchi, H;Hikage, M;Fukumoto, M
通讯作者：
Fukumoto, M