Heat shock‐induced heme oxygenase‐1 expression in a mouse hepatoma cell line is dependent on HSF1 and modified by NRF2 and BACH1
Heat shock‐induced heme oxygenase‐1 expression in a mouse hepatoma cell line is dependent on HSF1 and modified by NRF2 and BACH1
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小鼠肝癌细胞系中热休克诱导的血红素加氧酶-1 表达依赖于 HSF1，并受 NRF2 和 BACH1 修饰
DOI：
10.1111/gtc.12986
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发表时间：
2022
期刊：
影响因子：
2.1
通讯作者：
Akagi Reiko
中科院分区：
文献类型：
--
作者：
Inouye Sachiye;Kubo Takanori;Miyamoto Takafumi;Iyoda Takuya;Okita Naoyuki;Akagi Reiko
热休克（HS）诱导血红素加氧酶-1（HO-1）的机制尚不清楚。在这里，我们发现HS激活小鼠肝癌细胞系（Hepa 1-6）中的HO-1表达。敲除实验表明HS诱导的HO-1表达依赖于HS因子1（HSF 1）。染色质免疫沉淀（ChIP）试验证明HS激活的HSF 1与上游增强子1区（E1）的HS元件（HSE）结合。出乎意料的是，HS还促进BTB和CNC同源1（BACH 1）与E1中的Maf识别元件（MARE）结合。我们检查了催化失活的CRISPR相关9核酸酶（dCas 9）与短向导RNA（sgRNA）的作用，并证明了HSF 1与E1中的HSE结合对于HS诱导的HO-1表达是必不可少的。血红素处理（HA）使BACH 1与MARE分离，并促进核因子-红细胞-2-相关因子2（NRF 2）与MARE结合。在用HS和HA处理后，在E1中最显著地观察到HO-1诱导和HSF 1与HSE的结合。这些结果表明，HS诱导的HO-1表达依赖于HSF 1与E1中HSE的结合，尽管在同一E1中受到BACH 1和NRF 2与MARE结合的调节。
The induction mechanism of heme oxygenase‐1 (HO‐1) by heat shock (HS) is still unknown. Here, we discovered that HS activates the HO‐1 expression in a mouse hepatoma cell line (Hepa 1–6). Knockdown experiments showed that the HS‐induced HO‐1 expression was dependent on HS factor 1 (HSF1). A chromatin immunoprecipitation (ChIP) assay demonstrated that the HS‐activated HSF1 bound to the HS elements (HSEs) in the upstream enhancer 1 region (E1). Unexpectedly, HS also facilitates the BTB and CNC homology 1 (BACH1) binding to the Maf recognition elements (MAREs) in E1. We examined the effects of a catalytically inactive CRISPR‐associated 9 nucleases (dCas9) with short guide RNAs (sgRNAs), and demonstrated that the HSF1 binding to HSEs in E1 was indispensable for the HS‐induced HO‐1 expression. Heme treatment (HA) dissociates BACH1 from MAREs and facilitated the binding of nuclear factor‐erythroid‐2‐related factor 2 (NRF2) to MAREs. Following treatment with both HS and HA, the HO‐1 induction and the HSF1 binding to HSEs in E1 were most notably observed. These results indicate that the HS‐induced HO‐1 expression is dependent on the HSF1 binding to HSEs in E1, although modulated by the BACH1 and NRF2 binding to MAREs within the same E1.
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影响因子：
17.1
作者：
Arosio, Paolo;Mueller, Thomas;Knowles, Tuomas P. J.
通讯作者：
Knowles, Tuomas P. J.
影响因子：
4.1
作者：
Ikeda, H;Serria, MS;Sakai, M
通讯作者：
Sakai, M
DOI：
10.1073/pnas.88.12.5364
发表时间：
1991-06-01
影响因子：
11.1
作者：
EWING, JF;MAINES, MD
通讯作者：
MAINES, MD
影响因子：
11.4
作者：
Ogawa, K;Sun, J;Igarashi, K
通讯作者：
Igarashi, K
DOI：
10.1073/pnas.94.20.10919
发表时间：
1997-09-30
影响因子：
11.1
作者：
Poss, KD;Tonegawa, S
通讯作者：
Tonegawa, S