目的探讨不同剂量亚砷酸钠对人永生化角质形成细胞(human keratinocytes cell,Ha Ca T)Kelch样环氧氯丙烷相关蛋白-1(Keap1)和核转录因了红细胞系-2 p45相关因子-2(Nrf2)基因表达的影响。方法将Ha Ca T细胞分别暴露于终浓度为0(对照)、1...目的探讨不同剂量亚砷酸钠对人永生化角质形成细胞(human keratinocytes cell,Ha Ca T)Kelch样环氧氯丙烷相关蛋白-1(Keap1)和核转录因了红细胞系-2 p45相关因子-2(Nrf2)基因表达的影响。方法将Ha Ca T细胞分别暴露于终浓度为0(对照)、1.30、3.25、6.50μmol/L的亚砷酸钠培养基中培养24、48、72 h。采用流式细胞仪检测Ha Ca T细胞凋亡率,采用实时荧光定量(real-time quantitative PCR)检测Ha Ca T细胞中Nrf2、Keap1 m RNA的表达水平。结果与对照组相比,1.30μmol/L亚砷酸钠染毒24 h后Ha Ca T细胞的凋亡率降低,而3.25、6.50μmol/L亚砷酸钠染毒48、72 h后Ha Ca T细胞的凋亡率升高,差异均有统计学意义(P<0.05);且随着亚砷酸钠染毒时间的延长和染毒剂量的升高,Ha Ca T细胞的凋亡率均呈上升趋势。与对照组相比,1.30μmol/L亚砷酸钠染毒24、48、72 h和3.25μmol/L亚砷酸钠染毒24 h后Ha Ca T细胞中Nrf2 m RNA的表达水平均增高,而3.25、6.50μmol/L亚砷酸钠染毒72 h后Ha Ca T细胞中Nrf2 m RNA的表达水平均下降,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒时间的延长和染毒剂量的升高,Ha Ca T细胞Nrf2 m RNA的表达水平均呈下降趋势。与对照组相比,1.30、3.25μmol/L亚砷酸钠染毒72 h和3.25、6.50μmol/L亚砷酸钠染毒48 h后Ha Ca T细胞中Keap1 m RNA的表达水平均增高,差异有统计学意义(P<0.05)。随着亚砷酸钠染毒时间的延长,1.30μmol/L亚砷酸钠染毒组Ha Ca T细胞中Keap1 m RNA的表达水平呈波动性上升,3.25μmol/L亚砷酸钠染毒组Ha Ca T细胞中Keap1 m RNA的表达水平呈逐渐上升趋势,6.50μmol/L亚砷酸钠染毒组Ha Ca T细胞中Keap1 m RNA的表达水平呈先上升后下降;随着亚砷酸钠染毒剂量的升高,24、72 h时Ha Ca T细胞中Keap1 m RNA的表达水平呈下降趋势,而48 h时Ha Ca T细胞中Keap1 m RNA的表达水平呈上升趋势。结论亚砷酸钠可抑制Ha Ca T细胞的生长,诱导凋亡和角化的发生,其机制可�展开更多
The treatment of microglial BV-2 cells with sodium arsenate（As（V）：0.1-400 μmol/L — 48 hr）induces a dose-dependent response.The neurotoxic effects of high concentrations of As（V）（100,200 and 400 μmol/L） are...The treatment of microglial BV-2 cells with sodium arsenate（As（V）：0.1-400 μmol/L — 48 hr）induces a dose-dependent response.The neurotoxic effects of high concentrations of As（V）（100,200 and 400 μmol/L） are characterized by increased levels of mitochondrial complexesⅠ,Ⅱ,and Ⅳ followed by increased superoxide anion generation.Moreover,As（V） triggers an apoptotic mode of cell death,demonstrated by an apoptotic SubG1 peak,associated with an alteration of plasma membrane integrity.There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP.It is therefore tempting to speculate that As（V） triggers mitochondrial dysfunction,which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage,which in turn induces an apoptotic mode of cell death.展开更多
文摘目的探讨不同剂量亚砷酸钠对人永生化角质形成细胞(human keratinocytes cell,Ha Ca T)Kelch样环氧氯丙烷相关蛋白-1(Keap1)和核转录因了红细胞系-2 p45相关因子-2(Nrf2)基因表达的影响。方法将Ha Ca T细胞分别暴露于终浓度为0(对照)、1.30、3.25、6.50μmol/L的亚砷酸钠培养基中培养24、48、72 h。采用流式细胞仪检测Ha Ca T细胞凋亡率,采用实时荧光定量(real-time quantitative PCR)检测Ha Ca T细胞中Nrf2、Keap1 m RNA的表达水平。结果与对照组相比,1.30μmol/L亚砷酸钠染毒24 h后Ha Ca T细胞的凋亡率降低,而3.25、6.50μmol/L亚砷酸钠染毒48、72 h后Ha Ca T细胞的凋亡率升高,差异均有统计学意义(P<0.05);且随着亚砷酸钠染毒时间的延长和染毒剂量的升高,Ha Ca T细胞的凋亡率均呈上升趋势。与对照组相比,1.30μmol/L亚砷酸钠染毒24、48、72 h和3.25μmol/L亚砷酸钠染毒24 h后Ha Ca T细胞中Nrf2 m RNA的表达水平均增高,而3.25、6.50μmol/L亚砷酸钠染毒72 h后Ha Ca T细胞中Nrf2 m RNA的表达水平均下降,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒时间的延长和染毒剂量的升高,Ha Ca T细胞Nrf2 m RNA的表达水平均呈下降趋势。与对照组相比,1.30、3.25μmol/L亚砷酸钠染毒72 h和3.25、6.50μmol/L亚砷酸钠染毒48 h后Ha Ca T细胞中Keap1 m RNA的表达水平均增高,差异有统计学意义(P<0.05)。随着亚砷酸钠染毒时间的延长,1.30μmol/L亚砷酸钠染毒组Ha Ca T细胞中Keap1 m RNA的表达水平呈波动性上升,3.25μmol/L亚砷酸钠染毒组Ha Ca T细胞中Keap1 m RNA的表达水平呈逐渐上升趋势,6.50μmol/L亚砷酸钠染毒组Ha Ca T细胞中Keap1 m RNA的表达水平呈先上升后下降;随着亚砷酸钠染毒剂量的升高,24、72 h时Ha Ca T细胞中Keap1 m RNA的表达水平呈下降趋势,而48 h时Ha Ca T细胞中Keap1 m RNA的表达水平呈上升趋势。结论亚砷酸钠可抑制Ha Ca T细胞的生长,诱导凋亡和角化的发生,其机制可�
基金supported by grants from the University of Bourgogne(Dijon,France)the University of Monastir(Monastir,Tunisia)
文摘The treatment of microglial BV-2 cells with sodium arsenate（As（V）：0.1-400 μmol/L — 48 hr）induces a dose-dependent response.The neurotoxic effects of high concentrations of As（V）（100,200 and 400 μmol/L） are characterized by increased levels of mitochondrial complexesⅠ,Ⅱ,and Ⅳ followed by increased superoxide anion generation.Moreover,As（V） triggers an apoptotic mode of cell death,demonstrated by an apoptotic SubG1 peak,associated with an alteration of plasma membrane integrity.There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP.It is therefore tempting to speculate that As（V） triggers mitochondrial dysfunction,which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage,which in turn induces an apoptotic mode of cell death.
