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.

在我们以前的研究中，我们已经部分阐明了辐射诱导人外周血T细胞凋亡的机制。到目前为止，辐射诱导的活性氧簇（ROS）形成的确切位点尚不清楚。因此，在本研究中，我们利用MitoCapture H2 DCFDA（二氯二氢荧光素二乙酸酯的琥珀酰亚胺酯）、DAPI和Lysosensor研究了ROS形成的位点。我们的结果表明，活性氧的形成显然起源于线粒体和/或溶酶体，而不是在核辐射的T细胞。此外，在5戈伊照射T细胞后1 h观察到溶酶体肿胀和变形，可能揭示了溶酶体膜的不稳定性。5戈伊照射后4 h，可见溶酶体周围荧光增强，可能为溶酶体损伤。基于上述结果，我们得出结论，可能存在一个新的凋亡级联反应，涉及早期溶酶体膜不稳定的辐射诱导的人外周血T细胞凋亡。因此，溶酶体中羟基自由基形成引起的溶酶体蛋白酶泄漏（可能导致线粒体膜不稳定）的可能参与被认为在辐射诱导的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