A lipophilic free radical initiator, 2,2′-azobis (2,4-dimethylvaleronitrile) (AMVN) enhances caspase-dependent apoptosis induced by hyperthermia

A lipophilic free radical initiator, 2,2′-azobis (2,4-dimethylvaleronitrile) (AMVN) enhances caspase-dependent apoptosis induced by hyperthermia
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亲脂性自由基引发剂 2,2-偶氮双 (2,4-二甲基戊腈) (AMVN) 可增强热疗诱导的 caspase 依赖性细胞凋亡

DOI:
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发表时间:
2003
影响因子:
3.1
通讯作者:
L. Feril, jr
L. Feril, jr
中科院分区:
医学2区
文献类型:
--
作者:
F.;T. Kondo;Q.;Y. Hayashi;R. Ogawa;Zheng;L. Feril, jr

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目的:2,2 '-偶氮二(2-脒基丙烷)去盐酸盐(AAPH)是一种自由基引发剂,它能促进高温引起的细胞凋亡。在这里,但更亲脂的自由基引发剂,2,2 '-偶氮二(2,4-二甲基戊腈)(AMVN)被研究其作为可能的热敏化剂的效果。材料与方法:本研究采用高温联合不同浓度的AMVN处理人髓性单核细胞白血病U937细胞,观察其诱导细胞凋亡的能力,并通过多种参数来确定其诱导凋亡的途径。结果如下:高温与AMVN联合处理可明显诱导DNA片段化,而单纯高温或AMVN处理可诱导边缘性DNA片段化。部分细胞表现出较低的线粒体膜电位和增加超氧化物的产生后,联合治疗。使用各种胱天蛋白酶抑制剂和胱天蛋白酶3活性的荧光监测器的实验表明,胱天蛋白酶作用于线粒体的上游和下游。结论:AMVN是一种潜在的热致敏剂,在较低的浓度下比AAPH有效。讨论了可能的机理。
Purpose: A free radical initiator, 2,2'-azobis (2-amidinopropane) dehydrochloride (AAPH), was previously found to enhance apoptosis by hyperthermia. Here, but more lipophilic free radical initiator, 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) was investigated for its effects as a possible heat sensitizer. Materials and methods: Human myelogenous monocytic leukaemia U937 cells were treated with hyperthermia combined with a various concentration of AMVN for investigating its ability to induce apoptosis and various parameters to identify the pathway. Results: Combined treatment of hyperthermia and AMVN induced DNA fragmentation markedly, while hyperthermia or AMVN alone induced marginal DNA fragmentation. Fractions of cells showed low mitochondrial membrane potential and increased superoxide production after the combined treatment. Experiments using various caspase inhibitors and a fluorogenic monitor of caspase 3 activities indicated that caspase acts both up- and down-stream of mitochondria. Conclusions: AMVN is suggested to be a potential heat sensitizer effective at a lower concentration than AAPH. The possible mechanism is discussed.
伽马射线照射的基因诱导导致淋巴细胞中的 DNA 断裂。
DOI: --
发表时间: 1987
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Sellins,KS;Cohen,JJ
通讯作者: Cohen,JJ
DOI: 10.1021/bi9808262
发表时间: 1998-09-29
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
Fabisiak, JP;Tyurina, YY;Kagan, VE
通讯作者: Kagan, VE