聚胺耗竭延迟大鼠肠道上皮细胞的凋亡。
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Ray RM Viar MJ,元Q,约翰逊LR
聚胺耗竭延迟大鼠肠道上皮细胞的凋亡。
杂志的细胞杂志。2000年3月,278 (3):C480-9。
- PubMed ID
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10712236 (在PubMed]
- 文摘
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多胺的亚精胺、精胺和腐胺前体是必不可少的细胞生长和细胞周期的调控。最近的研究表明,过度积累多胺支持恶性转化或凋亡,根据细胞类型和刺激。本研究检视的参与多胺诱导的细胞凋亡的DNA拓扑异构酶抑制剂,喜树碱。在IEC-6细胞,喜树碱诱导细胞凋亡在6 h,伴随着细胞的分离。分离细胞显示DNA梯法和半胱天冬酶3感应,细胞凋亡的特征。损耗的腐胺、亚精胺和精胺,DL-alpha-difluoromethylornithine (DFMO),特定抑制剂的鸟氨酸脱羧酶(ODC)是第一个病原反应酶的聚胺生物合成,减少凋亡指数。延迟凋亡伴随着减少半胱天冬酶3活动polyamine-depleted细胞。添加腐胺恢复了诱导细胞凋亡的分离细胞的数量的增加和半胱天冬酶3活动。聚胺耗竭没有改变半胱天冬酶3蛋白的水平。由一个特定抑制剂抑制S-adenosylmethionine脱羧酶(diethylglyoxal bis - (guanylhydrazone); DEGBG] led to depletion of spermidine and spermine with a significant accumulation of putrescine and induction of ODC. The DEGBG-treated cells showed an increase in apoptosis, suggesting the importance of putrescine in the apoptotic process. Addition of putrescine to DFMO-treated cell extracts did not increase caspase 3 activity. The above results indicate that polyamine depletion delays the onset of apoptosis in IEC-6 cells and confers protection against DNA damaging agents, suggesting that polyamines might be involved in the caspase activating signal cascade.