Loss of STAT3 in mouse embryonic fibroblasts reveals its Janus-like actions on mitochondrial function and cell viability.
Loss of STAT3 in mouse embryonic fibroblasts reveals its Janus-like actions on mitochondrial function and cell viability.
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DOI：
10.1016/j.cyto.2013.12.006
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发表时间：
2014-03
期刊：
影响因子：
3.8
通讯作者：
Booz, George W.
中科院分区：
文献类型：
--
作者：
Zouein, Fouad A.;Duhe, Roy J.;Arany, Istvan;Shirey, Kristin;Hosler, Jonathan P.;Liu, Huiling;Saad, Iman;Kurdi, Mazen;Booz, George W.
STAT3 与线粒体功能有关；然而，这种作用的生理相关性尚未确定。在这里，我们研究了 STAT3 对细胞对刺激、TNFα 和血清剥夺的反应的重要性，这些刺激增加了线粒体活性氧 (ROS) 的形成。使用野生型 (WT) 和 STAT3 敲除 (KO) 小鼠胚胎成纤维细胞 (MEF) 进行实验。 WT 和 STAT3 KO MEF 均表达相似水平的肿瘤坏死因子受体 1 (TNFR1)，并且表现出与 TNFα 相当的 IκBα 降解。然而，在没有 STAT3 的情况下，TNFα 导致 NFκB p65 的核积累减弱，并且存活蛋白 c-FLIPL 的诱导被消除。尽管如此，WT MEF 对 TNFα 诱导的坏死更敏感。 STAT3 的缺失减少了 TNFα 和血清剥夺诱导的 ROS 形成。 STAT3 缺失与较低水平的复合物 I 和呼吸速率相关。相对于 WT 细胞，STAT3 KO 细胞的线粒体响应氧化应激释放显着更多的细胞色素 c，并且由于血清剥夺而具有更多的 caspase 3 裂解。我们的研究结果与 STAT3 通过确保线粒体完整性和促生存基因的表达而对线粒体功能和细胞活力很重要的观点一致。
STAT3 has been implicated in mitochondrial function; however, the physiological relevance of this action is not established. Here we studied the importance of STAT3 to the cellular response to stimuli, TNFα and serum deprivation, which increase mitochondrial reactive oxygen species (ROS) formation. Experiments were performed using wild type (WT) and STAT3 knockout (KO) mouse embryonic fibroblasts (MEF). Both WT and STAT3 KO MEF expressed similar levels of tumor necrosis factor receptor 1 (TNFR1) and exhibited comparable IκBα degradation with TNFα. However, in the absence of STAT3 nuclear accumulation of NFκB p65 with TNFα was attenuated and induction of the survival protein c-FLIPL was eliminated. Nonetheless, WT MEF were more sensitive to TNFα-induced death which was attributed to necrosis. Deletion of STAT3 decreased ROS formation induced by TNFα and serum deprivation. STAT3 deletion was associated with lower levels of complex I and rates of respiration. Relative to WT cells, mitochondria of STAT3 KO cells released significantly more cytochrome c in response to oxidative stress and had greater caspase 3 cleavage due to serum deprivation. Our findings are consistent with STAT3 being important for mitochondrial function and cell viability by ensuring mitochondrial integrity and the expression of pro-survival genes.
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影响因子：
9.5
作者：
Boengler K;Hilfiker-Kleiner D;Heusch G;Schulz R
通讯作者：
Schulz R
影响因子：
3.1
作者：
Boengler, Kerstin;Ungefug, Elvira;Schulz, Rainer
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Schulz, Rainer
影响因子：
3.3
作者：
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通讯作者：
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影响因子：
4.8
作者：
Esteve, JM;Mompo, J;Pallardó, FV
通讯作者：
Pallardó, FV
影响因子：
3.1
作者：
Camporeale, Annalisa;Poli, Valeria
通讯作者：
Poli, Valeria