NF-κB regulates HSF1 and c-Jun activation in heat stress-induced intestinal epithelial cell apoptosis
NF-κB regulates HSF1 and c-Jun activation in heat stress-induced intestinal epithelial cell apoptosis
复制标题
DOI：
10.3892/mmr.2017.8199
复制
发表时间：
2018-02-01
影响因子：
3.4
通讯作者：
Su, Lei
中科院分区：
文献类型：
--
作者：
Li, Jun;Liu, Yanan;Su, Lei
热应激可诱导肠上皮细胞凋亡，但其分子机制尚未明确。本研究采用IEC-6大鼠小肠上皮细胞研究热应激诱导的活性氧（ROS）的产生，其可能参与热应激期间核因子（NF）-κ B（B）的激活。IEC-6细胞转染NF-κ B B p65特异性小干扰RNA（siRNA），并观察到细胞凋亡和caspase-3裂解的显着增加;然而，在细胞转染腺病毒组成型过表达p65，得到相反的结果。此外，p65敲低增加了热应激诱导的热休克转录因子1（HSF 1）的表达和活性;相反，p65过表达轻微降低HSF 1的活性。还检查了热应激诱导的c-Jun磷酸化水平：p65的敲低导致c-Jun磷酸化减少，而p65过表达导致磷酸化增加。此外，siRNA介导的IEC-6细胞中HSF 1的敲低显著增加热应激诱导的凋亡。用c-Jun肽（c-Jun活化的抑制剂）预处理的细胞表现出凋亡的显著减少。这些结果表明，热应激刺激IEC-6细胞诱导NF-κ B B通过调节HSF 1和c-Jun激活的促凋亡作用。
Heat stress may induce intestinal epithelial cell apoptosis; however, the molecular mechanisms have not yet been identified. The present study used IEC-6 rat small intestinal epithelial cells to investigate heat stress-induced production of reactive oxygen species (ROS), which may be involved in nuclear factor (NF)-kappa B activation during heat stress. IEC-6 cells were transfected with NF-kappa B p65-specific small interfering RNA (siRNA), and observed a significant increase in cell apoptosis and caspase-3 cleavage; however, in cells transfected with adenovirus that constitutively overexpressed p65, the opposite results were obtained. Furthermore, p65 knockdown increased the heat stress-induced expression and activity of heat shock transcription factor 1 (HSF1); conversely, p65 overexpression slightly decreased HSF1 activity. The levels of heat stress-induced c-Jun phosphorylation were also examined: Knockdown of p65 resulted in a reduction of c-Jun phosphorylation, whereas p65 overexpression resulted in increased phosphorylation. Furthermore, siRNA-mediated knockdown of HSF1 in IEC-6 cells significantly increased heat stress-induced apoptosis. Cells pretreated with c-Jun peptide, an inhibitor of c-Jun activation, exhibited a significant reduction in apoptosis. These findings indicated that heat stress stimulation in IEC-6 cells induced the pro-apoptotic role of NF-kappa B by regulating HSF1 and c-Jun activation.