Apoptosis of alveolar epithelial cells induced by environmental polluting substances and it's signal transmission mechanisms.

环境污染物质诱导肺泡上皮细胞凋亡及其信号传递机制.

• 批准号: 06670382
• 负责人: TAKANO Yasuo
• 金额: $ 1.41万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670382/
• 关键词: Environmental Polluting Substances; Alveolar Type II Epithelial Cells; Cytotoxicity; Apoptosis; 重金属; 肺胞上皮細胞; 初代培養細胞

To examine the effect of environmental polluting substances on respiratory cells, we measured cytotoxicity of heavy metals, such as nickel, cdmium, mercury, lead, and manganese in primary culture of alveolar type II epithelial cells.Cytotoxic potency of mercury was more intensive than of cadmium, however, both these metals demonstrated a dose-dependent increase of the cytotoxicity. There was no difference among the compounds of the heavy metals in the cytotoxic potency. Under the same conditions, nickel, lead, and manganese revealed no cytotoxic effect. Nickel completely inhibited a metabolic activity of mitochondria. Screening of lung toxicity by detecting the primary culture of alveolar type II epithelial cells was efficient, simple, and highly reproducible procedure.To explain the mechanism of cell death induced by heavy metals, we studied the effect of them on damage of nuclear DNA in alveolar type II epithelial cells. The fragmentation of DNA,which is detected in apoptotic cells, was significantly induced in cells exposed by nickel. Follwed by mercury and cadmium, nickel was demonstrated as the most potent alter agent by rank order of the fragmentation of DNA.The fragmentation of DNA induced by lead and manganese remained unaffected. Amount of fragmentation of DNA in cells exposed by nickel decreased without cells' death after 6 hours of exposure. It, therefore, indicated that mechanisms that provide reparation of DNA may start just after DNA was damaged.These results are indicating that the sensitivity of alveolar type II epithelial cells to the cytotoxicity induced by heavy metals is different. Moreover, evidence suggest that expression of mechanisms of the cytotoxicity varies and depends on heavy metal.

为了研究环境污染物质对呼吸细胞的影响，我们测量了原代培养肺泡II型上皮细胞中重金属（如镍、镉、汞、铅和锰）的细胞毒性。汞的细胞毒性比镉更强，然而，这两种金属的细胞毒性都呈剂量依赖性增加。各重金属化合物的细胞毒力无明显差异。在相同的条件下，镍、铅和锰没有显示出细胞毒性作用。镍完全抑制了线粒体的代谢活动。通过检测肺泡II型上皮细胞的原代培养来筛选肺毒性是一种高效、简单和高度可重复性的方法。为了解释重金属诱导细胞死亡的机制，我们研究了重金属对肺泡II型上皮细胞核DNA损伤的影响。在镍暴露的细胞中，凋亡细胞中检测到的DNA片段明显诱导。其次是汞和镉，镍被证明是最有效的改变剂排序的DNA碎片。铅和锰诱导的DNA断裂未受影响。暴露于镍后6小时，细胞DNA断裂量减少，但细胞未死亡。因此，这表明提供DNA修复的机制可能在DNA受损后才开始。这些结果提示肺泡II型上皮细胞对重金属细胞毒性的敏感性存在差异。此外，有证据表明，细胞毒性的表达机制是不同的，并依赖于重金属。