Differential Gene Expression in Rat Vascular Smooth Muscle Cells Following Treatment with Coptisine Exerts a Selective Antiproliferative Effect
Differential Gene Expression in Rat Vascular Smooth Muscle Cells Following Treatment with Coptisine Exerts a Selective Antiproliferative Effect
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DOI：
10.1021/np100645d
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发表时间：
2011-04-01
影响因子：
5.1
通讯作者：
Inoue, Makoto
中科院分区：
文献类型：
--
作者：
Suzuki, Hiroka;Tanabe, Hiroki;Inoue, Makoto
已知黄连碱（1），一种异喹啉生物碱，选择性抑制大鼠原代血管平滑肌细胞（VSMCs）的增殖。本研究观察了其对几种平滑肌样细胞增殖抑制作用的特点，并与小檗碱（2）和巴马汀（3）的作用进行了比较。为了进一步阐明1的VSMC选择性抗增殖作用的机制，通过确定哪些mRNA显示受1调节的表达来研究负责的基因。黄连碱（1）对主动脉平滑肌细胞的抗增殖作用强于其他器官平滑肌细胞。mRNA表达分析显示，1上调两个基因，生长停滞和DNA损伤诱导α（Gadd 45 a）和响应：补体32基因（Rgc 32）。这两个基因在3 Y1成纤维细胞中保持不变，并且不受2和3的影响。黄连碱（1）可诱导Gadd 45 a和Rgc 32基因的mRNA表达，尤其是在VSMC中。1激活这些基因可能介导细胞周期进程的抑制。然而，由于这些基因通常在不同的表达。细胞类型，可能存在1个活性的选择性靶。upstream;：of these genes.
It is known that coptisine (1), an isoquinoline alkaloid, selectively inhibits proliferation of rat primary vascular smooth muscle cells,(VSMCs). In the present study, the characteristics of its antiproliferative effect on several types of smooth muscle like cells were investigated and compared to the effects of berberine (2) and palmatine (3). TO Clarify further the mechanism underlying the VSMC-selective, antiproliferative effect of 1; the genes responsible were investigated by determining which mRNAs showed expression regulated by 1. Coptisine (1) showed greater antiproliferative effect on smooth muscle cells derived from the aorta than on those derived from other organs. Analysis of the MRNA expression revealed that 1 upregulated two genes, growth arrest and DNA-damage-inducible alpha (Gadd45a) and response: gene to Complement32 (Rgc32). Both genes remained unchanged in 3Y1 fibroblasts and were not affected by 2 and 3. Coptisine (l) was found to induce the mRNA of the Gadd45a and Rgc32 genes, Specifically in VSMC. Activation of these genes by 1 may Mediate inhibition of cell cycle progression. However, as these genes tare commonly expressed in various. Cell types, a selective target for 1 activity is likely to exist.; upstream;:of these genes..