The mechanism of heme oxygenase-1 (HO-1) induction by heat shock (HS) loading remains unclear. Here, we investigated the contribution of transcription factors to HS-induced HO-1 expression, using a rat hepatoma cell line (H-4-II-E). Our results demonstrated that HS treatment resulted in a marked induction of HO-1. Immunohistochemical analysis showed a slight mismatch in the expression levels of HO-1 and HSP70 by HS among cells, suggesting a conflict between multiple induction mechanisms. We observed HS-induced nuclear localization of, not only phosphorylated HSF1, but also NRF2, which is a typical transcription factor activated by oxidative stress. HSF1 knockdown in H-4-II-E markedly reduced HO-1 induction by HS, while NRF2 knockdown resulted in a partial effect.

中文翻译：

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大鼠肝癌细胞系热休克诱导的血红素加氧酶-1 受 HSF1、NRF2 和 BACH1 的协同作用调节

热休克 (HS) 负荷诱导血红素加氧酶-1 (HO-1) 的机制尚不清楚。在这里，我们使用大鼠肝癌细胞系 (H-4-II-E) 研究了转录因子对 HS 诱导的 HO-1 表达的贡献。我们的结果表明 HS 处理导致 HO-1 的显着诱导。免疫组织化学分析显示细胞间HS对HO-1和HSP70的表达水平略有不匹配，表明多种诱导机制之间存在冲突。我们观察到 HS 诱导的核定位，不仅是磷酸化的 HSF1，还有 NRF2，这是一种典型的由氧化应激激活的转录因子。H-4-II-E 中的 HSF1 敲低显着降低了 HS 对 HO-1 的诱导，而 NRF2 敲低导致部分效果。