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.

为了更好地理解血红素氧合酶(HO)-1作为细胞对非热低强度脉冲超声波(LIPUS，0.3W/cm~2，1min)和轻度高温(MH，41℃，30min)反应的分子机制，我们利用高密度寡核苷酸芯片和计算基因表达分析检测了人类淋巴瘤U937细胞的基因表达模式和遗传网络。LIPUS作用6h后，细胞凋亡率为(14±3.8)%，未见细胞溶解。在分析的22,283组探针中，LIPUS下调了193个基因，上调了201个基因，上调了1.5倍。MH作用3h后，细胞内423个基因表达上调，515个基因表达下调，但未诱导细胞凋亡。在LIPUS和MH处理的细胞中发现了显著的遗传网络，并观察到HO-1与NRG1或NF2、BCL2或CREB1相互作用。当细胞受到X射线照射时，在17937细胞中观察到HO-1的上调，而在HeLa细胞中则没有。本结果表明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。识别与HO-1相互作用的辐射反应基因仍然是未来研究的主题。

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

Ultrasound enhances liposome-mediated gene transfection

• DOI: 10.1016/j.ultsonch.2004.06.006
• 发表时间: 2005-08-01
• 期刊: ULTRASONICS SONOCHEMISTRY
• 影响因子: 8.4
• 作者: Feril, LB;Ogawa, R;Kondo, T
• 通讯作者: Kondo, T

Genetic networks responsive to sodium butyrate in colonic epithelial cells

• DOI: 10.1016/j.febslet.2006.04.048
• 发表时间: 2006-05-29
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Tabuchi, Yoshiaki;Takasaki, Ichiro;Kondo, Takashi
• 通讯作者: Kondo, Takashi

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.