Mechanism of Generation of Reactive Oxygen Species from Mitochondria by Nuclear Signal

核信号从线粒体产生活性氧的机制

• 批准号: 16390541
• 负责人: MAJIMA Hideyuki
• 金额: $ 9.34万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390541/
• 关键词: Mitochondria; Superoxide; Apoptosis; Nuclear genome; 検出法; 蛍光試薬; ミトコンドリア障害; 活性酸素; 核シグナル; 突然変異; シャペロン; p53; HSP70

Reactive oxygen species (ROS) seem to be an inducer of various diseases and pathogenesis such as aging, neuro-degenerative diseases, i.e., Alzheimer's disease, Parkinson's disease etc. Since we have reported the first evidence that mitochondrial generation of ROS controls apoptosis (Majima et al. JBC 1998), we have investigated the relationship between ROS and apoptosis, caused by radiation, blue light exposure, ischemia reperfusion, chemotherapeutic agent treatments (bleomycin and cis-platinum). In every experiments tested, we have confirmed the relationship among ROS, lipid peroxidation and apoptosis.In this study, we further investigated nuclear genome activation in mitochondrial DNA lacking cells (Rho0 cells) by DNA microarray, and found out that 402 genes out of 2236 nuclear genes were changed in Rho0 cells, suggesting a possible cross-talk messengers between mitochondria and nucleus. To test a possible role of p53 and hsp70 on the cross-talk messenger, we suppressed mRNA expression level by these RNAi, and studied change of ROS generation from mitochondria. A positive increase in ROS by transfection of MnSOD RNAi vectors was found, while no change of ROS by transfection of p53 or hsp70 RNAi vectors were revealed, suggesting p53 and HSP70 are not candidate of the cross-talk messenger.

活性氧簇(ROS)似乎是各种疾病和致病机制的诱因，如衰老、神经退行性疾病，即阿尔茨海默病、帕金森氏病等。JBC 1998)，我们研究了ROS与辐射、蓝光照射、缺血再灌注、化疗药物(博莱霉素和顺铂)引起的细胞凋亡的关系。在每一次实验中，我们都证实了ROS、脂质过氧化和细胞凋亡之间的关系。在本研究中，我们进一步利用DNA芯片研究了线粒体DNA缺失细胞(Rho0细胞)的核基因组激活，发现在Rho0细胞中2236个核基因中有402个基因发生了变化，提示线粒体和细胞核之间可能存在串扰信使。为了测试P53和HSP70在串音信使中的可能作用，我们通过这些RNAi抑制了mRNA的表达水平，并研究了线粒体产生ROS的变化。转染MnSOD RNAi载体后ROS明显增加，而P53和HSP70 RNAi载体对ROS无明显影响，提示P53和HSP70不是串扰信使。

项目成果

Oxidative Stress, Disease and Cancer (Singh KK, editor)

氧化应激、疾病和癌症（Singh KK，编辑）

• 发表时间: 2006
• 作者: Majima HJ;Indo HP;Tomita K;Suenaga S;Motoori S;Kato H;Yen H-C;Ozawa T
• 通讯作者: Ozawa T

Evaluation of anti-platelet aggregatory effects of aspirin, cilostazol and ramatroban on platelet-rich plasma and whole blood

• DOI: 10.1097/00001721-200403000-00007
• 发表时间: 2004-03-01
• 期刊: BLOOD COAGULATION & FIBRINOLYSIS
• 影响因子: 1.1
• 作者: Kariyazono, H;Nakamura, K;Yamada, K
• 通讯作者: Yamada, K

Increased expression of humaanin peptide in diffuse type pigmented villonodular synovitis : implication of its mitochondrial abnormality

弥散型色素沉着绒毛结节性滑膜炎中人氨肽表达增加：其线粒体异常的意义

• 发表时间: 2005
• 期刊: Annals of the Rheumatic diseases 64・6
• 作者: Ohira Y;Kawano F;Wang X.D;Sudoh M;Iwashita Y;Majima HJ;Nonaka I;Ijiri K
• 通讯作者: Ijiri K

Enhancement of Cisplatin-induced apoptosis and caspase 3 activation by depletion of mitochondrial DNA in a human osteosarcoma cell line

通过消耗人骨肉瘤细胞系中的线粒体 DNA 增强顺铂诱导的细胞凋亡和 caspase 3 激活

• 发表时间: 2005
• 期刊: Annals of the New York Academy of Sciences 1042
• 作者: Ohira Y;Kawano F;Wang X.D;Sudoh M;Iwashita Y;Majima HJ;Nonaka I;Ijiri K;Kakinuma S;Yen HC;Yen HC
• 通讯作者: Yen HC

Levels of reactive oxygen species and primary antioxidant enzymes in WI38 versus trasformed WI38 cells following bleomcyin treatment

博莱霉素处理后 WI38 细胞与转化 WI38 细胞中活性氧和主要抗氧化酶的水平

• 发表时间: 2005
• 期刊: Free Radical Biology & Medicine 38・7
• 作者: Ohira Y;Kawano F;Wang X.D;Sudoh M;Iwashita Y;Majima HJ;Nonaka I;Ijiri K;Kakinuma S;Yen HC
• 通讯作者: Yen HC