Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells.
Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells.
复制标题
DOI：
10.1186/1423-0127-19-29
复制
发表时间：
2012-03-09
影响因子：
11
通讯作者：
Yang KT
中科院分区：
文献类型：
--
作者：
Chiu SC;Huang SY;Tsai YC;Chen SP;Pang CY;Lien CF;Lin YJ;Yang KT
睡眠呼吸暂停综合征患者睡眠时间歇性气流停止导致间歇性低氧(IH)。我们的目的是研究IH对小脑颗粒细胞的影响，并探讨IH诱导细胞死亡的机制。小脑颗粒细胞新鲜取自新生SD大鼠。将小脑颗粒细胞培养在氧气浓度为20%和5%的孵箱中，每30分钟振荡一次，持续1-4天。这项研究的结果是基于使用共聚焦显微镜和相关软件进行的图像分析。细胞氧化应激随IH的增加而增加。此外，细胞死亡(细胞凋亡和坏死)的发生随着IH持续时间的增加而增加，但在铁螯合剂(邻菲咯啉)或聚(ADP-核糖)聚合酶(PARP)抑制剂[3-氨基苯甲酰胺(3-AB)和DPQ]存在的情况下减少。无论IH持续时间长短，caspase-3的荧光强度均保持不变，Western blotts未检测到caspase-3的激活。然而，IH增加了凋亡诱导因子(AIF)移位到细胞核的比例，而PARP抑制剂(3-AB)降低了这一比例。根据我们的发现，IH增加了氧化应激，并随后导致细胞死亡。这种作用至少部分地由PARP激活，导致ATP耗竭，Calain激活，导致AIF移位到细胞核。我们认为，IH通过刺激氧化应激、PARP介导的Calain和AIF激活来诱导大鼠小脑颗粒细胞死亡。
Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death. Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O2 concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio. According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus. We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.
登录
查看更多内容
影响因子：
4.2
作者：
Fujimoto, N;Minowa, K;Adachi-Usami, E
通讯作者：
Adachi-Usami, E
影响因子：
--
作者：
Liu, Al-Ling;Wang, Xin-Wei;Yan, Guang-Mei
通讯作者：
Yan, Guang-Mei
DOI：
10.1073/pnas.0606526103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Andrabi, Shaida A.;Kim, No Soo;Dawson, Ted M.
通讯作者：
Dawson, Ted M.
影响因子：
5.3
作者：
Vosler, Peter S.;Sun, Dandan;Wang, Suping;Gao, Yanqin;Kintner, Douglas B.;Signore, Armando P.;Cao, Guodong;Chen, Jun
通讯作者：
Chen, Jun
DOI：
10.1073/pnas.0606528103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Yu, Seong-Woon;Andrabi, Shaida A.;Dawson, Valina L.
通讯作者：
Dawson, Valina L.