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通过多聚腺苷酸(Poly (A))抑制视网膜母细胞瘤mRNA降解参与黄连素对脑缺血的神经保护作用。

Inhibition of retinoblastoma mRNA degradation through Poly (A) involved in the neuroprotective effect of berberine against cerebral ischemia.

作者信息

Chai Yu-Shuang, Yuan Zhi-Yi, Lei Fan, Wang Yu-Gang, Hu Jun, Du Feng, Lu Xi, Jiang Jing-Fei, Xing Dong-Ming, Du Li-Jun

机构信息

MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.

Department of Neuro-Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States of America.

出版信息

PLoS One. 2014 Mar 6;9(6):e90850. doi: 10.1371/journal.pone.0090850. eCollection 2014.

Abstract

Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.

摘要

小檗碱是一种异喹啉生物碱,对缺血神经元具有抗凋亡作用。为了解释这些活性,本研究对小檗碱在神经元缺血/再灌注过程中诱导的细胞周期停滞进行了研究。根据体外氧糖剥夺神经元和体内脑缺血/再灌注的ICR小鼠实验,发现小檗碱可通过其对聚腺苷酸(poly(A))尾的作用保护视网膜母细胞瘤(Rb)的mRNA不被降解。视网膜母细胞瘤1(Rb基因,RB1)mRNA水平的半衰期延长确保了视网膜母细胞瘤蛋白水平,这有助于神经元在缺血/再灌注过程中细胞周期停滞,从而避免细胞进入凋亡过程。RB1 mRNA的聚腺苷酸尾作为小檗碱新发现的靶点,有助于人们关注小檗碱与mRNA之间的相互作用,以进一步了解小檗碱的生物学活性和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3407/3946351/f7454eef6faa/pone.0090850.g001.jpg

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