Chloroquine exacerbates serum withdrawal-induced G(1) phase arrest via an autophagy-independent mechanism
Chloroquine exacerbates serum withdrawal-induced G(1) phase arrest via an autophagy-independent mechanism
复制标题
氯喹通过不依赖自噬的机制加剧血清戒断诱导的 G(1) 期停滞
DOI：
10.1039/c7ra06737b
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发表时间：
2017
期刊：
影响因子：
3.9
通讯作者：
Liu Zhongmin
中科院分区：
文献类型：
--
作者：
Gao Lei;Zhu Hongming;Fan Huimin;Liu Zhongmin
氯喹（CQ）是临床上广泛使用的抗疟或辅助治疗药物。然而，其对缺血内皮细胞的作用尚不清楚。在此，我们发现血清戒断诱导人脐静脉内皮细胞G1期阻滞和自噬。此外，CQ加剧了血清戒断诱导的G1期阻滞，而Atg 5敲低的自噬抑制没有。Akt和MEK 1/2/ERK 1/2的通路分析验证了CQ和Atg 5敲低之间的细胞周期差异。此外，CQ还加剧了Atg 5敲低的细胞中血清戒断诱导的G1期阻滞。通过采用谷胱甘肽，活性氧清除剂，我们证实，CQ增强细胞内的氧化应激在血清戒断加重G1期阻滞。因此，我们证明，CQ加剧血清撤退诱导的G1期停滞通过自噬独立，但在内皮细胞的氧化应激依赖性机制。
Chloroquine (CQ) is a widely used anti-malaria or complementary drug in the clinic. However, its effect on ischemic endothelial cells remains unclear. Herein, we showed that serum withdrawal induced G1 phase arrest and autophagy in human umbilical vein endothelial cells. Moreover, CQ exacerbated serum withdrawal-induced G1 phase arrest, whereas autophagy inhibition by Atg5 knockdown did not. Pathway analyses of Akt and MEK1/2/ERK1/2 verified the cell cycle difference between CQ and Atg5 knockdown. Additionally, CQ also exacerbated serum withdrawal-induced G1 phase arrest in the cells with Atg5 knockdown. Through employing glutathione, a reactive oxygen species scavenger, we confirmed that CQ-enhanced intracellular oxidative stress during serum withdrawal aggravated G1 phase arrest. We thus demonstrate that CQ exacerbates serum withdrawal-induced G1 phase arrest via an autophagy-independent, but an oxidative stress-dependent mechanism in endothelial cells.