• 关键词：亚砷酸钠  酵母  细胞死亡  NO

• 基金项目：国家自然科学基金项目(No.30870454,30470318);山西省实验动物专项(No.200811)

• 吴丽华
• 1. 太原师范学院 生物系, 太原 030031;
  2. 山西大学生命科学学院, 太原 030006

• 仪慧兰
• 山西大学生命科学学院, 太原 030006

• 张虎芳
• 太原师范学院 生物系, 太原 030031

• 摘要：以模式生物酵母细胞为材料,研究亚砷酸钠胁迫对细胞死亡率和胞内NO水平的影响,以探讨NO在砷诱导细胞死亡中的作用.结果显示,浓度为1~7mmol·L^-1的亚砷酸钠可降低酵母细胞活性,诱导细胞死亡,随着处理浓度的升高和作用时间的延长,细胞死亡率增高;死细胞出现核固缩和核降解等凋亡特征;凋亡抑制剂Z-Asp-CH₂-DCB(2μmol·L^-1)与3mmol·L^-1亚砷酸钠共同作用后,酵母细胞死亡率下降.在亚砷酸钠胁迫的过程中,酵母细胞内NO水平升高;一定浓度的NO清除剂c-PTIO(0.2mmol·L^-1)或NO生成抑制剂NaN₃(1mmol·L^-1)均可降低亚砷酸钠引起的酵母细胞死亡率.结果表明,砷胁迫诱导的胞内NO升高是酵母细胞死亡的一个诱因,亚砷酸钠诱发的酵母细胞死亡中可能存在细胞凋亡过程.

• Abstract：Arsenic is a toxic metalloid widely distributed in the environment.Chronic exposure to arsenic is associated with increased risk of various diseases,such as neurotoxicity,birth defects and metabolic disorders.People exposed to high levels of arsenic are prone to skin,bladder,and lung cancer and occlusive vascular disease.However,the exact mechanisms of arsenic toxicity are not yet well understood.In this study,cytotoxic effects of sodium arsenite on yeast Saccharomyces cerevisiae were investigated with or without some antagonists.For arsenic treatments,yeast cells harvested from the early log phase were incubated in the fresh yeast extract peptone dextrose (YPD) media containing varying amounts of sodium arsenite.For other combination treatments,selected antagonists including broad caspase inhibitor Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-CH₂-DCB),nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-1-oxyl-3-oxide (c-PTIO) and nitrate reductase inhibitor NaN₃ were respectively added into YPD media in the presence of 3 mmol·L^-1 sodium arsenite.The results showed that sodium arsenite exposure decreased cell viability in a dose-and time- dependent manner.Exposure to 1 to 7 mmol·L^-1 arsenite for 3 to 24 h significantly induced cell death.Dead cells showed some typical features of apoptosis,such as nuclear condensation and fragmentation.Caspase inhibitor Z-Asp-CH₂-DCB (2 SymbolmA@ mol·L^-1) significantly blocked arsenite-induced cell death.The characteristic features of apoptosis and the blockade by apoptosis inhibitor suggested a process of programmed cell death in arsenite-treated yeast cells.Arsenite exposure induced significant cell death and also an obvious increase of intercellular NO levels.Moreover,when either NO scavenger c-PTIO (0.2 mmol·L^-1) or NR inhibitor NaN₃(1 mmol·L^-1) was used to block intracellular NO increase,arsenite-induced cell death significantly decreased.These results clearly demonstrated that arsenite-caused cell death is associated with an increase of the intercellular NO levels.Increased NO triggered arsenite-induced cell death,and may also contribute to arsenite-induced programmed cell death.Our results suggest that arsenite-induced cell death may have dual effects on the organism,since apoptosis is programmed cell death for the good of the organism,but other kinds of cell death may be harmful to the body.

• Key words：sodium arsenite  yeast  cell death  NO

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