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.

在我们前期的研究中，我们部分阐明了辐射诱导人外周T细胞凋亡的机制。迄今为止，辐射诱导的 ROS（活性氧）形成的确切位置尚不清楚。因此，在本研究中，我们利用 MitoCapture H2DCFDA（二氯二氢荧光素二乙酸琥珀酰亚胺酯）、DAPI 和 Lysosensor 来研究 ROS 形成位点。我们的结果表明，ROS 的形成显然起源于线粒体和/或溶酶体，而不是受辐射的 T 细胞的细胞核。此外，在 T 细胞 5 Gy 照射后 1 小时观察到溶酶体肿胀和畸形，可能揭示了溶酶体膜的不稳定。 5 Gy 辐照后 4 小时，观察到溶酶体周围的荧光增加，可能表明溶酶体破裂。基于上述结果，我们得出结论，在辐射诱导的人外周T细胞凋亡中，可能存在涉及早期溶酶体膜不稳定的新的凋亡级联反应。因此，溶酶体中羟基自由基形成引起的溶酶体蛋白酶渗漏（可能导致线粒体膜不稳定）被认为在辐射诱导的 T 细胞凋亡中发挥重要作用。

项目成果

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

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

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)

Mechanism of hydrogen peroxide-induced apoptosis of the human osteosarcoma cell line HS-Os-1

过氧化氢诱导人骨肉瘤细胞HS-Os-1凋亡的机制

• 发表时间: 2003
• 期刊: International Journal of Molecular Medicine 12
• 作者: Ogawa Y.;et al.;小川 恭弘;小川 恭弘;小川 恭弘;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