Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression.
Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression.
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DOI：
10.1016/j.bbrc.2015.06.027
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发表时间：
2015-08
影响因子：
3.1
通讯作者：
H. Kikuchi;F. Kuribayashi;H. Mimuro;S. Imajoh‐ohmi;Masami Nakayama;Y. Takami;H. Nishitoh;T. Nakayama
中科院分区：
文献类型：
--
作者：
H. Kikuchi;F. Kuribayashi;H. Mimuro;S. Imajoh‐ohmi;Masami Nakayama;Y. Takami;H. Nishitoh;T. Nakayama
内质网（endoplasmic reticulum，ER）是一种复杂的膜结构，在真核细胞中具有重要的作用.内质网功能的突变会导致内质网应激，从而引起癌症、神经退行性疾病、糖尿病等多种疾病，长期的内质网应激可通过激活多种信号转导途径引发细胞凋亡。为了研究组蛋白乙酰转移酶GCN 5在调节ER应激中的生理作用，我们分析了纯合GCN 5缺陷型DT 40突变体Δ GCN 5对ER应激的反应。DT 40中GCN 5缺陷引起对药理学ER应激剂（毒胡萝卜素和衣霉素）诱导的细胞凋亡的强烈抵抗。使用特异性Bcl-2抑制剂的药物分析表明，对长期ER应激诱导的细胞凋亡的强烈抵抗部分是由于Δ GCN 5中Bcl-2基因表达的上调。这些数据表明，GCN 5通过控制Bcl-2基因的表达参与调节延长的ER应激诱导的细胞凋亡。
The endoplasmic reticulum (ER), a complex membrane structure, has important roles in all eukaryotic cells. Catastrophe of its functions would lead to ER stress that causes various diseases such as cancer, neurodegenerative diseases, diabetes and so on. Prolonged ER stress could trigger apoptosis via activation of various signal transduction pathways. To investigate physiological roles of histone acetyltransferase GCN5 in regulation of ER stress, we analyzed responses of homozygous GCN5-deficient DT40 mutants, ΔGCN5, against ER stress. GCN5-deficiency in DT40 caused drastic resistance against apoptosis induced by pharmacological ER stress agents (thapsigargin and tunicamycin). Pharmaceutical analysis using specific Bcl-2 inhibitors showed that the drastic resistance against prolonged ER stress-induced apoptosis is, in part, due to up-regulation of Bcl-2 gene expression in ΔGCN5. These data revealed that GCN5 is involved in regulation of prolonged ER stress-induced apoptosis through controlling Bcl-2 gene expression.