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Cigarette smoke extract and heated tobacco products promote ferritin cleavage and iron accumulation in human corneal epithelial cells
Scientific Reports ( IF 4.6 ) Pub Date : 2021-09-17 , DOI: 10.1038/s41598-021-97956-3
Wataru Otsu 1 , Kodai Ishida 1 , Naoki Chinen 2 , Shinsuke Nakamura 2 , Masamitsu Shimazawa 1, 2 , Hideshi Tsusaki 2 , Hideaki Hara 1, 2
Affiliation  

The cornea is directly exposed to cigarette smoke, and smoking is a risk factor for several corneal diseases including dry eye syndrome. Currently, heated tobacco products (HTPs) are widely used as substitutes for cigarette smoking around the world. In the present study, we investigated the molecular mechanism(s) leading to cellular injury induced by cigarette smoke extract (CSE) or HTPs. Exposure to CSE perturbed the formation of tight junctions, leading to an increase in cell volume, a decrease in transepithelial electrical resistance (TER) in the human corneal epithelial cell-transformed (HCE-T) cell line. Moreover, CSE exposure induced both lipid peroxidation and ferrous [Fe(II)] ion accumulation in autolysosomal compartments. Interestingly, a cleaved form of ferritin appeared when HCE-T cells were incubated with CSE. This aberrant ferritin processing was suppressed by treatment with autophagy inhibitors. Furthermore, the CSE-induced cell death was suppressed by either ferrostatin-1 or deferoxamine (DFO). CSE exposure also promoted the expression of cytokines whereas DFO treatment inhibited the CSE-induced expression of these cytokines. Exposure to HTPs also induced both HCE-T cell death and cleaved ferritin accumulation in a concentration- and time-dependent manner. These results indicated that CSE or HTPs activated the ferroptosis signaling pathway, which contributed to corneal epithelial cell injury.



中文翻译:

香烟烟雾提取物和加热烟草制品促进人角膜上皮细胞铁蛋白裂解和铁积累

角膜直接暴露在香烟烟雾中,吸烟是包括干眼症在内的几种角膜疾病的危险因素。目前,加热烟草制品 (HTP) 在世界范围内被广泛用作吸烟的替代品。在本研究中,我们研究了导致由香烟烟雾提取物 (CSE) 或 HTPs 诱导的细胞损伤的分子机制。暴露于 CSE 会扰乱紧密连接的形成,导致细胞体积增加,人角膜上皮细胞转化 (HCE-T) 细胞系中跨上皮电阻 (TER) 降低。此外,CSE 暴露诱导脂质过氧化和亚铁 [Fe(II)] 离子在自体溶酶体区室中积累。有趣的是,当 HCE-T 细胞与 CSE 一起孵育时,会出现一种裂解形式的铁蛋白。这种异常的铁蛋白加工被自噬抑制剂的治疗所抑制。此外,CSE 诱导的细胞死亡被 ferrostatin-1 或去铁胺 (DFO) 抑制。CSE 暴露也促进了细胞因子的表达,而 DFO 治疗抑制了 CSE 诱导的这些细胞因子的表达。暴露于 HTP 还以浓度和时间依赖性方式诱导 HCE-T 细胞死亡和裂解铁蛋白积累。这些结果表明CSE或HTPs激活了ferroptosis信号通路,导致角膜上皮细胞损伤。CSE 暴露也促进了细胞因子的表达,而 DFO 治疗抑制了 CSE 诱导的这些细胞因子的表达。暴露于 HTP 还以浓度和时间依赖性方式诱导 HCE-T 细胞死亡和裂解铁蛋白积累。这些结果表明CSE或HTPs激活了ferroptosis信号通路,导致角膜上皮细胞损伤。CSE 暴露也促进了细胞因子的表达,而 DFO 治疗抑制了 CSE 诱导的这些细胞因子的表达。暴露于 HTP 还以浓度和时间依赖性方式诱导 HCE-T 细胞死亡和裂解铁蛋白积累。这些结果表明CSE或HTPs激活了ferroptosis信号通路,导致角膜上皮细胞损伤。

更新日期:2021-09-17
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