Molecular mechanism of induction of hemeoxygenase-1 by radiation, hyperthermia , and ultrasound

辐射、热疗和超声诱导血红素加氧酶-1的分子机制

• 批准号: 17310032
• 负责人: KONDO Takashi
• 金额: $ 7.64万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17310032/
• 关键词: Radiation; Hyperthermia; Ultrasound; Microarray; Oxidative stress; アポトーシス; 過酸化水素; 一酸化窒素; アルキルラジカル; cDNAマイクロアレイ; 遺伝子発現

For better understanding of the molecular mechanism of hemeoxygenase (HO)-1 as a component of cellular response to non-thermal low intensity pulsed ultrasound(LIPUS, 0.3 W/cm2 for 1 min), and mild hyperthermia (MH, 41℃, 30 min), we examined gene expression patterns and genetic networks in human lymphoma U937 cells using high-density oligonucleotide microarrays and computational gene expression analyses. Six hours after LIPUS treatment, apoptosis (14±3.8%) with no cell lysis was observed. Of 22,283 probe sets analyzed, LIPUS down-regulated 193 genes and up-regulated 201 genes by >1.5-fold. On the other hand, 423 genes were up-regulated and 515 genes were down-regulated in the cells 3 h post-treatment with MH which did not induce apoptosis. The significant genetic networks were identified and the interaction between HO-1 and NRG1 or NF2, and BCL2 or CREB1 was observed in the cells treated with LIPUS and MH, respectively. When the cells were exposed to X-rays, up-regulation of HO-1 was observed in 17937 cells but not in HeLa cells.The present results indicate that LIPUS and MH affect the expression of many genes and provide novel insight into the biomolecular mechanisms of HO-1. The identification of radiation-responsive genes interacting with HO-1 remains a subject for future studies.

为了更好地了解血红素加氧酶 (HO)-1 作为细胞对非热低强度脉冲超声（LIPUS，0.3 W/cm2 1 分钟）和轻度热疗（MH，41℃，30分钟），我们使用高密度寡核苷酸微阵列和计算基因表达分析检查了人淋巴瘤 U937 细胞中的基因表达模式和遗传网络，LIPUS 处理后六小时，细胞凋亡。在分析的 22,283 个探针组中，观察到 (14±3.8%) 没有细胞裂解，LIPUS 下调 193 个基因，上调 201 个基因超过 1.5 倍。另一方面，423 个基因上调，515 个基因上调。 MH 处理后 3 小时，细胞中的基因下调，但不诱导细胞凋亡。确定了重要的遗传网络以及 HO-1 和 NRG1 或之间的相互作用。在用LIPUS和MH处理的细胞中分别观察到NF2、BCL2或CREB1。当细胞暴露于X射线时，在17937细胞中观察到HO-1的上调，但在HeLa细胞中没有观察到。表明 LIPUS 和 MH 影响许多基因的表达，并为 HO-1 的生物分子机制提供了新的见解。 HO-1 的辐射响应基因的鉴定仍然是一个课题。以便将来的学习。

项目成果

酸化ストレス フリーラジカル医学生物学の最前線

氧化应激：自由基医学生物学的前沿

• 发表时间: 2006
• 作者: 工藤 信樹;近藤 隆;近藤 隆
• 通讯作者: 近藤 隆

Analysis of gene expression in apoptosis of human lymphoma U937 cells induced by heat shock and the effects of a-phenyl N-tert-butylnitrone(PBN)andits derivatives.

热激诱导人淋巴瘤U937细胞凋亡基因表达及α-苯基-N-叔丁基硝酮(PBN)及其衍生物的影响分析

• 发表时间: 2005
• 期刊: Apoptosis 10
• 作者: Hirano H.;et. al.
• 通讯作者: et. al.

Identification of gene responsive to paeoniflorin, a heat shock protein-inducing compound, in human leukemia U937 cells.

鉴定人白血病 U937 细胞中对芍药苷（一种热休克蛋白诱导化合物）有反应的基因。

• 发表时间: 2007
• 期刊: Int. J. Hyperthermia 23
• 作者: Salunga T. L.;e al.
• 通讯作者: e al.

Enhancement of hyperthermia-induced apoptosis by a new synthesized class of fhran-fused tetracyclic compounds.

一类新合成的 fhran 融合四环化合物增强热疗诱导的细胞凋亡。

• 发表时间: 2007
• 期刊: Apoptosis 12
• 作者: Yu D.-Y.;et. al.
• 通讯作者: et. al.

Idetification of genes responsive to low intensity pulsed ultrasound in a human leukemia cell line Molt-4.

识别人类白血病细胞系 Molt-4 中对低强度脉冲超声敏感的基因。

• 发表时间: 2007
• 期刊: Cancer Lett. 246
• 作者: Tabuchi Y.;et. al.
• 通讯作者: et. al.