Reactive oxygen species producing site in radiation-induced apoptosis of human peripheral T cells: Involvement of lysosomal membrane destabilization

辐射诱导的人外周 T 细胞凋亡中活性氧的产生位点：溶酶体膜不稳定的参与

• 批准号: 15591281
• 负责人: OGAWA Yasuhiro
• 金额: $ 2.24万
• 依托单位: KOCHI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591281/
• 关键词: lymphocyte; T lymphocyte; apoptosis; lysosome; radiation; mitochondria

In our previous studies, we have partly elucidated the mechanism of radiation-induced apoptosis of human peripheral T cells. The exact site of the ROS (reactive oxygen species) formation induced by irradiation has been so far unknown. Therefore, in this study, we investigated the site of ROS formation by utilizing MitoCapture H2DCFDA (succinimidyl ester of dichlorodihydrofluorescein diacetate), DAPI, and Lysosensor. Our results showed that ROS formation apparently originated in the mitochondria and/or lysosomes instead of in the neclei of irradiated T cells. Moreover, lysosomal swelling and deformity, possibly revealing lysosomal membrane instability, were observed at 1 h after 5 Gy irradiation of T cells. At 4 h after irradiatronof 5 Gy, increase of fluorescence around the lysosomes, possibly revealing lysosomal ruputure, was seen. Based on the above results, we concluded the possible existence of a new apoptotic cascade involving early lysosomal membrane destabilization in radiation-induced apoptotsis of human peripheral T cells. Therefore, possible involvement of lysosomal protease leakage caused by hydroxyl radical formation in lysosomes (possibly resulting in mitochondrial membrane destabilization) is considered to play an important role in radiation induced T cell apoptosis.

在我们之前的研究中，我们已经部分阐明了辐射诱导人外周T细胞凋亡的机制。到目前为止，辐射诱导产生的ROS(活性氧物种)的确切位置还不清楚。因此，在本研究中，我们利用MitoCapture H_2DCFDA(二氯二氢荧光素二乙酸酯的琥珀酰亚胺酯)、DAPI和溶酶传感器来研究ROS的形成部位。我们的结果表明，ROS的形成明显起源于线粒体和/或溶酶体，而不是辐射后T细胞的细胞核。5GyT细胞照射后1h可见溶酶体肿胀和变形，可能是溶酶体膜不稳定的表现。5Gy射线照射后4h，溶酶体周围荧光增强，可能显示溶酶体皱缩。基于以上结果，我们得出结论，在辐射诱导的人外周T细胞凋亡中，可能存在一个新的涉及早期溶酶体膜失稳的凋亡级联反应。因此，溶酶体内产生羟基自由基(可能导致线粒体膜失稳)引起的溶酶体蛋白水解酶泄漏被认为在辐射诱导T细胞凋亡中起重要作用。

项目成果

Prevention of hydrogen peroxide-induced apoptosis of human peripheral T cells by a lysosomotropic iron chelator, ammonium..

通过溶酶体铁螯合剂铵预防过氧化氢诱导的人外周 T 细胞凋亡。

• 发表时间: 2004
• 期刊: International Journal of Molecular Medicine 14
• 作者: 小川 恭弘;小川 恭弘;小川 恭弘
• 通讯作者: 小川 恭弘

Reactive oxygen species-producing site in radiation-induced apoptosis of human peripheral T cells : Involvement of lysosomal.

辐射诱导的人外周 T 细胞凋亡中活性氧的产生位点：溶酶体的参与。

• 发表时间: 2004
• 期刊: International Journal of Molecular Medicine 13
• 作者: Ogawa Y.;et al.;小川 恭弘
• 通讯作者: 小川 恭弘

小川恭弘: "Comparison of radiation-induced reactive oxygen species formation in adult articular chondrocytes and that in human peripheral T cells"Int.J.Mol.Med.. 11. 455-459 (2003)

Yasuhiro Okawa：“成人关节软骨细胞和人外周 T 细胞中辐射诱导的活性氧形成的比较”Int.J.Mol.Med.. 11. 455-459 (2003)

Immunocytochemical characteristics of human osteosarcoma cell line HS-Os-1 : Possible implication in apoptotic resistance...

人骨肉瘤细胞系 HS-Os-1 的免疫细胞化学特征：对细胞凋亡抵抗的可能影响...

• 发表时间: 2004
• 期刊: International Journal of Molecular Medicine 14
• 作者: 小川 恭弘;小川 恭弘
• 通讯作者: 小川 恭弘

Prevention of hydrogen peroxide-induced apoptosis of human peripheral T cells by a lysosomotropic iron chelator, ammonium.

通过溶酶体铁螯合剂铵预防过氧化氢诱导的人外周 T 细胞凋亡。

• 发表时间: 2004
• 期刊: International Journal of Molecular Medicine 14
• 作者: Ogawa Y.;et al.;小川 恭弘;小川 恭弘;小川 恭弘
• 通讯作者: 小川 恭弘