Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC
| العنوان: | Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC |
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| المؤلفون: | Hajime Kusano, Richard Chikara Koya, Shinji Kamada, Hisakazu Fujita, Yoshihide Tsujimoto, Noboru Kuzumaki, Shigeomi Shimizu |
| المصدر: | Oncogene. 19:4807-4814 |
| بيانات النشر: | Springer Science and Business Media LLC, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Cancer Research, Voltage-dependent anion channel, Recombinant Fusion Proteins, bcl-X Protein, Porins, Apoptosis, Mitochondria, Liver, macromolecular substances, Mitochondrion, Transfection, Jurkat Cells, Mice, Species Specificity, Apoptotic mitochondrial changes, Genetics, Animals, Humans, Voltage-Dependent Anion Channels, skin and connective tissue diseases, Molecular Biology, Gelsolin, Chelating Agents, Ion Transport, biology, 3T3 Cells, musculoskeletal system, Actins, Mitochondria, Neoplasm Proteins, Protein Structure, Tertiary, Rats, Cell biology, Proto-Oncogene Proteins c-bcl-2, Liposomes, biology.protein, Calcium, sense organs, HeLa Cells |
| الوصف: | Gelsolin is a Ca2+-dependent actin-regulatory protein that modulates actin assembly and disassembly, and is believed to regulate cell motility through modulation of the actin network. Gelsolin was also recently suggested to be involved in the regulation of apoptosis: human gelsolin (hGsn) has anti-apoptotic activity, whereas mouse gelsolin (mGsn) exerts either proapoptotic or anti-apoptotic activity depending on different cell types. Here, we studied the basis of anti-apoptotic activity of hGsn. We showed that both endogenous and overexpressed hGsn has anti-apoptotic activity, that depends on its C-terminal half. We also found that hGsn and its C-terminal half but not mGsn could prevent apoptotic mitochondrial changes such as Apsi loss and cytochrome c release in isolated mitochondria to a similar extent as Bcl-xL, indicating that hGsn targets the mitochondria to prevent apoptosis via its C-terminal half. In the same way as anti-apoptotic Bcl-xL, which we recently found to prevent apoptotic mitochondrial changes by binding and closing the voltage-dependent anion channel (VDAC), hGsn and its C-terminal half inhibited the activity of VDAC on liposomes through direct binding in a Ca2+-dependent manner. These results suggest that hGsn inhibits apoptosis by blocking mitochondrial VDAC activity. |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c31769986ac3d1aaf8e6bfb183b6665 https://doi.org/10.1038/sj.onc.1203868 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8c31769986ac3d1aaf8e6bfb183b6665 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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