Evaluation of effects of aldehyde dehydrogenase on oxidative stress

乙醛脱氢酶对氧化应激影响的评价

• 批准号: 19310043
• 负责人: KUNUGITA Naoki
• 金额: $ 8.57万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19310043/
• 关键词: アルデヒド脱水素酵素; 酸化ストレス; ヘモグロビン付加体; Aldh2ノックアウトマウス; アセトアルデヒド; ミトコンドリアDNA; 体細胞突然変異; 加齢; 変異原性

Aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde produced from ethanol into acetate and plays a major role in the oxidation of acetaldehyde in vivo. Half of Japanese have inactive ALDH2. In order to investigate the mutagenicity of acetaldehyde, micronucleus (MN) assay and T cell receptor (TCR) gene mutation assay were performed in Aldh2 KO mice and wild type (Aldh2 WT) mice exposed to acetaldehyde or ethanol in vivo. We also observed the urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), hemoglobin-associated acetaldehyde (Hb-AA), and mutation on tRNA gene of mitochondrial DNA. In results, frequencies of micronuclei in reticulocytes significantly increased by acetaldehyde exposure in Aldh2 KO mice, but not in Aldh2 WT mice. In addition, frequencies of micronuclei, TCR mutation, and 8-OHdG levels in urine were significantly high in Aldh2 KO mice than in Aldh2 WT mice even in control groups. These results indicate that Aldh2 plays a major role not only in acetaldehyde detoxification but also in oxidative stress in mice.

乙醛脱氢酶-2（ALDH 2）将乙醇产生的乙醛代谢为乙酸，并在体内乙醛氧化中起主要作用。一半的日本人有不活跃的ALDH 2。为了研究乙醛的致突变性，在体内暴露于乙醛或乙醇的Aldh 2 KO小鼠和野生型（Aldh 2 WT）小鼠中进行微核（MN）试验和T细胞受体（TCR）基因突变试验。同时观察尿8-羟基脱氧鸟苷（8-OHdG）、血红蛋白相关乙醛（Hb-AA）及线粒体DNA tRNA基因突变。结果显示，Aldh 2 KO小鼠的网织红细胞微核率在乙醛暴露后显著增加，但在Aldh 2 WT小鼠中未增加。此外，即使在对照组中，Aldh 2 KO小鼠的微核频率、TCR突变和尿液中8-OHdG水平也显著高于Aldh 2 WT小鼠。这些结果表明，Aldh 2不仅在乙醛解毒中起重要作用，而且在小鼠的氧化应激中也起重要作用。

项目成果

Evaluatlon of formaldehyde exposure during a gross anatomy dissection course

大体解剖过程中甲醛暴露的评估

• 发表时间: 2007
• 期刊: Prooeedmgs of IAQVEC 2007 II
• 作者: Kunugita N;Mei N;Goncharova T;Norimura T.;Naoki KUNUGITA;Naoki KUNUGITA
• 通讯作者: Naoki KUNUGITA

STAT5 is activated in formaldehyde-exposed mice.

STAT5 在接触甲醛的小鼠中被激活。

• 发表时间: 2009
• 作者: 吉田安宏;Ding Ning;野口順子;欅田尚樹;杉浦勉
• 通讯作者: 杉浦勉

アルデヒド脱水素酵素2ノックアウトの呼吸器系組織におけるアセトアルデヒド感受性

乙醛脱氢酶2敲除呼吸组织中的乙醛敏感性

• 发表时间: 2007
• 作者: 小山倫浩;一瀬豊日;PHAM Thi Thu Phuong;小川真規;山口哲右;木長健;八嶋康典;尾崎真一;松本明子;市場正良;欅田尚樹;川本俊弘
• 通讯作者: 川本俊弘

Characteristics of aldehyde dehydrogenase 2 (Aldh2) knockout mice

• DOI: 10.3109/15376510903401708
• 发表时间: 2009-11
• 期刊: Toxicology Mechanisms and Methods
• 影响因子: 3.2
• 作者: Hsu-Sheng Yu;T. Oyama;T. Isse;Kyoko Kitakawa;M. Ogawa;T. Pham;T. Kawamoto

Strain differences influence N-methyl-D-aspartate receptor subunit gene expression in the olfactory bulb of an allergic mouse model following toluene exposure

品系差异影响甲苯暴露后过敏小鼠模型嗅球中 N-甲基-D-天冬氨酸受体亚基基因表达

• 发表时间: 2010
• 期刊: Neuroimmunomodulation
• 影响因子: 2.4
• 作者: Win-Shwe TT;Kunugita N;Yamamoto S;Arashidani K;Fujimaki H
• 通讯作者: Fujimaki H