title: Differential gene expression in rat vascular smooth muscle cells following treatment with coptisine exerts a selective antiproliferative effect.
abstract: 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 a 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 (1) 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 are commonly expressed in various cell types, a selective target for 1 activity is likely to exist upstream of these genes.
authors.affiliation: Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
authors.forename: Hiroka
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Hajime
authors.initials: H
authors.lastname: Mizukami
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D000097642:GADD45 Proteins
chemical_list: D001599:Berberine; D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins; C486417:Rgcc protein, rat; C034384:coptisine