Inhibition of telomerase causes vulnerability to endoplasmic reticulum stress-induced neuronal cell death.
Inhibition of telomerase causes vulnerability to endoplasmic reticulum stress-induced neuronal cell death.
复制标题
端粒酶的抑制导致内质网应激诱导的神经元细胞死亡的脆弱性。
DOI：
10.1016/j.neulet.2016.07.027
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ozawa K.
中科院分区：
文献类型：
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作者：
Hosoi T;Nakatsu K;Shimamoto A;Tahara H;Ozawa K.
内质网（ER）应激与多种疾病有关，如癌症和神经退行性疾病。在本研究中，我们调查了端粒酶在内质网应激诱导的细胞死亡的可能参与。ER应激诱导的细胞死亡在端粒酶逆转录酶（TERT）过表达的MCF 7细胞（MCF 7-TERT细胞）中得到改善。端粒酶特异性抑制剂BIBR 1532可逆转TERT对内质网应激诱导MCF 7-TERT细胞死亡的抑制作用。这些发现表明，BIBR 1532可能特异性抑制端粒酶活性，从而诱导ER应激暴露细胞的细胞死亡。TERT在SH-SY 5 Y神经母细胞瘤细胞系中表达。为了分析端粒酶可能参与ER应激诱导的神经元细胞死亡，我们用BIBR 1532处理SH-SY 5 Y神经母细胞瘤细胞，并分析ER应激诱导的细胞死亡。我们发现BIBR 1532显著增强ER应激诱导的神经元细胞死亡。这些发现表明，端粒酶活性的抑制可能会增加由ER应激引起的神经细胞死亡的脆弱性。
Endoplasmic reticulum (ER) stress is implicated in several diseases, such as cancer and neurodegenerative diseases. In the present study, we investigated the possible involvement of telomerase in ER stress-induced cell death. ER stress-induced cell death was ameliorated in telomerase reverse transcriptase (TERT) over-expressing MCF7 cells (MCF7-TERT cell). Telomerase specific inhibitor, BIBR1532, reversed the inhibitory effect of TERT on ER stress-induced cell death in MCF7-TERT cells. These findings suggest that BIBR1532 may specifically inhibit telomerase activity, thereby inducing cell death in ER stress-exposed cells. TERT was expressed in the SH-SY5Y neuroblastoma cell line. To analyze the possible involvement of telomerase in ER stress-induced neuronal cell death, we treated SH-SY5Y neuroblastoma cells with BIBR1532 and analyzed ER stress-induced cell death. We found that BIBR1532 significantly enhanced the ER stress-induced neuronal cell death. These findings suggest that inhibition of telomerase activity may enhance vulnerability to neuronal cell death caused by ER stress.