Involvement of caspase-3 and p38 mitogen-activated protein kinase in cobalt chloride-induced apoptosis in PC12 cells
文献类型：期刊论文
| 作者 | Zou, WG; Zeng, JP; Zhuo, M; Xu, WJ; Sun, LY; Wang, JX; Liu, XY |
| 刊名 | JOURNAL OF NEUROSCIENCE RESEARCH
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| 出版日期 | 2002 |
| 卷号 | 67期号:6页码:837-843 |
| 关键词 | PC12 cells cobalt chloride apoptosis p35 caspase-3 p38 MAPK |
| 通讯作者 | Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China., |
| 英文摘要 | Our previous study showed that cobalt chloride (CoCl2) could induce PC12 cell apoptosis and that the CoCl2- treated PC12 cells may serve as a simple in vitro model for the study of the mechanism of hypoxia-linked neuronal disorders. The aim of this study is to elucidate the mechanism of CoCl2-induced apoptosis in PC12 cells. Caspases are known to be involved in the apoptosis induced by various stimuli in many cell types. To investigate the involvement of caspases in CoCl2-induced apoptosis in PC12 cells, we generated PC12 cells that stably express the viral caspases inhibitor gene p35 and analyzed the effect of p35 on the process of apoptosis induced by CoCl2. We also examined the effect of cell-permeable peptide inhibitors of caspases. The results showed that the baculovirus p35 gene and the general caspases inhibitor Z-VAD-FMK significantly block apoptosis induced by CoCl2, confirming that caspase is involved in CoCl2-induced apoptosis. Further investigation showed that in this process the caspase-3-like activity is increased, as indicated by the cells' ability to cleave the fluorogenic peptide substrate Ac-Asp-Glu-Val-Asp-7-AMC and to degrade the DNA-repairing enzyme poly(ADP-ribose) polymerase (PARP), an endogenous caspase-3 substrate. At the same time, caspase-3-specific inhibitors, namely, the peptide Ac-DEVD-CHO, Ac-DEVD-FMK, partially inhibit CoCl2-induced apoptosis. These findings suggested that caspase-3 or caspase-3-like proteases are involved in the apoptosis induced by CoCl2 in PC12 cells. Additionally, we have observed that another apoptotic marker, p38 mitogen-activated protein kinase (MAPK), is significantly activated in this process in a time-dependent manner and that a selective p38 MAPK inhibitor, SB203580, partially inhibits this cell death. The addition of SB203580 also partially suppresses caspase-3-like activity. All these results confirm that the CoCl2-treated PC12 cell is a useful in vitro model with which to study hypoxia-linked neuronal disorders. Furthermore, the results showing that the baculovirus p35 gene and caspase inhibitors possess a remarkable ability to rescue PC12 cells from CoCl2- induced cell death may have implications for future neuroprotective therapeutic approaches for the hypoxia-associated disorders. (C) 2002 Wiley-Liss, Inc. |
| 学科主题 | Neurosciences & Neurology |
| 类目[WOS] | Neurosciences |
| 关键词[WOS] | CEREBELLAR GRANULE CELLS ; POLY(ADP-RIBOSE) POLYMERASE ; FAMILY PROTEASES ; BRAIN ; DEATH ; NEURONS ; HYPOXIA ; ISCHEMIA ; BCL-2 ; ICE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000174158700017 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2522]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zou, WG,Zeng, JP,Zhuo, M,et al. Involvement of caspase-3 and p38 mitogen-activated protein kinase in cobalt chloride-induced apoptosis in PC12 cells[J]. JOURNAL OF NEUROSCIENCE RESEARCH,2002,67(6):837-843. |
| APA | Zou, WG.,Zeng, JP.,Zhuo, M.,Xu, WJ.,Sun, LY.,...&Liu, XY.(2002).Involvement of caspase-3 and p38 mitogen-activated protein kinase in cobalt chloride-induced apoptosis in PC12 cells.JOURNAL OF NEUROSCIENCE RESEARCH,67(6),837-843. |
| MLA | Zou, WG,et al."Involvement of caspase-3 and p38 mitogen-activated protein kinase in cobalt chloride-induced apoptosis in PC12 cells".JOURNAL OF NEUROSCIENCE RESEARCH 67.6(2002):837-843. |
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