Heat Shock Induces IκB-α and Prevents Stress-Induced Endothelial Cell Apoptosis
Heat Shock Induces IκB-α and Prevents Stress-Induced Endothelial Cell Apoptosis
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热激诱导 IκB-α 并防止应激诱导的内皮细胞凋亡
DOI：
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
J. Cobb
中科院分区：
文献类型：
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作者：
S. L. DeMeester;T. Buchman;Y. Qiu;A. Jacob;K. Dunnigan;R. Hotchkiss;I. Karl;J. Cobb
目的：探讨预先热休克是否会减弱内皮细胞凋亡，以及是否通过核因子κ B和抑制剂κ B α介导了预先热休克的作用。设计：一项随机、对照的体外研究。环境：大型学术医疗中心的实验室。干预措施：增加亚砷酸钠剂量（40-160 μmol/L）处理培养的原代猪内皮细胞，之后发生凋亡（脂多糖-亚砷酸钠）侵袭的时间间隔不同（4-16小时）。分别采用中性红摄取法和膜联蛋白V染色法和碘化丙啶染色法测定细胞死亡和凋亡程度。Western blot法检测诱导热休克蛋白70和抑制剂κ B α水平。脂多糖诱导的核因子κ B活性采用电泳迁移率转移法进行评估。结果：先前的亚砷酸盐治疗降低了细胞凋亡，并呈时间和剂量依赖性。其中，较高的亚砷酸钠浓度和较短的时间间隔（P= 0.01, 160 μmol/L）对4 h的保护效果较好。对细胞凋亡的保护作用与热休克蛋白70和抑制剂kappa B α水平升高和核因子kappa B结合活性降低有关。结论：亚砷酸盐是热休克反应的诱导剂，可减少应激诱导的内皮细胞凋亡。这种保护机制可能包括降低核因子κ B活性或增加诱导热休克蛋白70水平。热休克蛋白70不仅可以作为一种分子标记来确定细胞的表型状态，还可以作为一种分子标记来确定热休克所提供的保护的持久性。这些数据支持了应激诱导的转录因子活性和蛋白表达变化可以调节细胞凋亡诱导的假设。Arch surgery . 1997；132:1283 - 1288
Objective: To determine whether prior heat shock would attenuate endothelial cell apoptosis and whether any effect of preemptive heat shock is mediated through a nuclear factor kappa B and inhibitor kappa B α mechanism. Design: A randomized, controlled in vitro study. Setting: A laboratory in a large, academic medical center. Interventions: Cultured primary porcine endothelial cells were treated with increasing doses of sodium arsenite (40-160 μmol/L), after which the interval until subsequent apoptotic (lipopolysaccharide-arsenite) challenge was varied (4-16 hours). The degree of cell death and apoptosis were determined using neutral red uptake and staining with annexin V and propidium iodide, respectively. Inducible heat shock protein 70 and inhibitor kappa B α levels in treated cells were determined by Western blot analysis. Lipopolysaccharide-induced nuclear factor kappa B activity was assessed using an electrophoretic mobility shift assay. Results: Prior arsenite treatment decreased cell death by apoptosis in a time- and dose-dependent manner. Specifically, a higher sodium arsenite concentration and shorter intervals afforded better protection (P=.01, 160 μmol/L at 4 hours). Protection against apoptosis correlated with increased heat shock protein 70 and inhibitor kappa B α levels and decreased nuclear factor kappa B binding activity. Conclusions: Arsenite, an inducer of the heat shock response, decreased stress-induced endothelial cell apoptosis. The mechanism of this protection may include decreased nuclear factor kappa B activity or increased inducible heat shock protein 70 levels. Heat shock protein 70 may serve as a molecular marker to determine not only the phenotypic state of the cell but also the durability of protection afforded by heat shock. These data support the hypothesis that stress-induced changes in transcription factor activity and protein expression can regulate the induction of apoptosis. Arch Surg. 1997;132:1283-1288
影响因子：
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作者：
P. A. Abello;S. Fidler;Gregory B. Bulkley;Timothy G. Buchman
通讯作者：
P. A. Abello;S. Fidler;Gregory B. Bulkley;Timothy G. Buchman
影响因子：
3.8
作者：
Jacob, AK;Hotchkiss, RS;Buchman, TG
通讯作者：
Buchman, TG