Cell type-specific upregulation of Parkin in response to ER stress.
Cell type-specific upregulation of Parkin in response to ER stress.
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DOI：
10.1089/ars.2006.1522
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发表时间：
2007-04
影响因子：
6.6
通讯作者：
Hua-Qin Wang;Y. Imai;A. Kataoka;R. Takahashi
中科院分区：
文献类型：
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作者：
Hua-Qin Wang;Y. Imai;A. Kataoka;R. Takahashi
Parkin 是导致家族性帕金森病 (PD) 的基因，称为常染色体隐性遗传青少年帕金森病 (AR-JP)/PARK2。 Parkin 已被证明可以保护细胞免受内质网 (ER) 应激和氧化应激，这可能是由于其泛素连接酶 (E3) 活性以蛋白酶体降解蛋白质为目标。尽管作者表明 Parkin 因 ER 应激而上调，但随后的报告表明，它并不代表普遍的未折叠蛋白反应 (UPR)。在这里，作者报告了不同细胞系中 Parkin 响应 ER 应激的不同调节，证明 Parkin 的上调是对 ER 应激的细胞类型特异性反应。 2-巯基乙醇 (2-ME) 和衣霉素可增加 SH-SY5Y (H) 细胞、Neuro2a 细胞、Goto-P3 细胞中 Parkin 的表达，但不增加 SH-SY5Y (J) 细胞和 IMR32 细胞中的 Parkin 表达。与这些研究同时进行的，ER 应激也观察到了 Parkin 共调节基因 (PACRG)/与 Parkin 相邻的基因 (Glup) 的类似上调。荧光素酶检测未能检测到 500 bp Parkin/Glup 启动子响应 ER 应激的转录激活。这些结果表明 ER 应激诱导 Parkin 代表细胞类型特异性反应。
Parkin is the gene responsible for a familial form of Parkinson's disease (PD) termed autosomal recessive juvenile parkinsonism (AR-JP)/PARK2. Parkin has been shown to protect cells from endoplasmic reticulum (ER) stress and oxidative stress, presumably due to its ubiquitin ligase (E3) activity that targets proteins for proteasomal degradation. Although the authors showed that parkin is upregulated in response to ER stress, subsequent reports suggest that it does not represent a universal unfolded protein response (UPR). Here the authors report different regulation of parkin in response to ER stress in different cell lines, demonstrating upregulation of parkin as a cell type-specific response to ER stress. 2-Mercaptoethanol (2-ME) and tunicamycin increased the expression of parkin in SH-SY5Y (H) cells, Neuro2a cells, Goto-P3 cells, but not in SH-SY5Y (J) cells and IMR32 cells. In parallel with these studies, similar upregulation of the parkin coregulated gene (PACRG)/gene adjacent to parkin (Glup) was also observed by ER stress. Luciferase assays failed to detect the transcriptional activation of 500 bp parkin/Glup promoter in response to ER stress. These results indicate that induction of parkin by ER stress represents a cell type-specific response.