Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells
Recently, it has been shown that endoplasmic reticulum (ER) stress causes apoptosis. However, the mechanism of the ER stress-dependent pathway is not fully understood. In human neuroblastoma SH-SY5Y cells, we detected a caspase-12-like protein that has a molecular mass (approximately 60 kDa) similar...
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| Format: | Article |
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Elsevier
2003-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319326544 |
| _version_ | 1818310855223148544 |
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| author | Yoshihisa Kitamura Atsushi Miyamura Kazuyuki Takata Masatoshi Inden Daiju Tsuchiya Kumi Nakamura Takashi Taniguchi |
| author_facet | Yoshihisa Kitamura Atsushi Miyamura Kazuyuki Takata Masatoshi Inden Daiju Tsuchiya Kumi Nakamura Takashi Taniguchi |
| author_sort | Yoshihisa Kitamura |
| collection | DOAJ |
| description | Recently, it has been shown that endoplasmic reticulum (ER) stress causes apoptosis. However, the mechanism of the ER stress-dependent pathway is not fully understood. In human neuroblastoma SH-SY5Y cells, we detected a caspase-12-like protein that has a molecular mass (approximately 60 kDa) similar to that of mouse caspase-12. Thapsigargin, an inhibitor of ER-associated Ca2+-ATPase, induced the degradation of caspase-12-like protein. In addition, the degradation of caspases-9 and -3, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and cell death were also observed. Pretreatment with phorbol-12-myristate-13-acetate, which induces the expression of antiapoptotic Bcl-2, inhibited thapsigargin-induced degradation of caspases-9 and -3, but not caspase-12-like protein degradation. A caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OCH3)-CH2F, inhibited the degradation of caspase-12-like protein, but not that of caspases-9 and -3. These results suggest that thapsigargin may induce the activation of both ER- and mitochondria-dependent pathways in human SH-SY5Y cells. |
| first_indexed | 2024-12-13T07:52:41Z |
| format | Article |
| id | doaj.art-12de6b2b2f50462087604c10c3731648 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-13T07:52:41Z |
| publishDate | 2003-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-12de6b2b2f50462087604c10c37316482022-12-21T23:54:36ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01923228236Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y CellsYoshihisa Kitamura0Atsushi Miyamura1Kazuyuki Takata2Masatoshi Inden3Daiju Tsuchiya4Kumi Nakamura5Takashi Taniguchi6Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanDepartment of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanDepartment of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanDepartment of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanDepartment of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanDepartment of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanDepartment of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, JapanRecently, it has been shown that endoplasmic reticulum (ER) stress causes apoptosis. However, the mechanism of the ER stress-dependent pathway is not fully understood. In human neuroblastoma SH-SY5Y cells, we detected a caspase-12-like protein that has a molecular mass (approximately 60 kDa) similar to that of mouse caspase-12. Thapsigargin, an inhibitor of ER-associated Ca2+-ATPase, induced the degradation of caspase-12-like protein. In addition, the degradation of caspases-9 and -3, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and cell death were also observed. Pretreatment with phorbol-12-myristate-13-acetate, which induces the expression of antiapoptotic Bcl-2, inhibited thapsigargin-induced degradation of caspases-9 and -3, but not caspase-12-like protein degradation. A caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OCH3)-CH2F, inhibited the degradation of caspase-12-like protein, but not that of caspases-9 and -3. These results suggest that thapsigargin may induce the activation of both ER- and mitochondria-dependent pathways in human SH-SY5Y cells.http://www.sciencedirect.com/science/article/pii/S1347861319326544 |
| spellingShingle | Yoshihisa Kitamura Atsushi Miyamura Kazuyuki Takata Masatoshi Inden Daiju Tsuchiya Kumi Nakamura Takashi Taniguchi Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells Journal of Pharmacological Sciences |
| title | Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells |
| title_full | Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells |
| title_fullStr | Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells |
| title_full_unstemmed | Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells |
| title_short | Possible Involvement of Both Endoplasmic Reticulumand Mitochondria-Dependent Pathways in Thapsigargin-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells |
| title_sort | possible involvement of both endoplasmic reticulumand mitochondria dependent pathways in thapsigargin induced apoptosis in human neuroblastoma sh sy5y cells |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319326544 |
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