Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, P.R. China.
Biol Pharm Bull. 2011;34(10):1527-32. doi: 10.1248/bpb.34.1527.
Gq-protein is located at the convergent point in signal transduction pathways leading to vascular remodeling. The carboxyl terminus of Gα-subunit plays a vital role in G-protein-receptor interaction. The present study was designed to explore the effects of a synthetic Gαq carboxyl terminus imitation peptide, namely GCIP-27, on vascular smooth muscle cells (VSMC) in vitro and vascular remodeling in spontaneous hypertensive rats (SHR). Hyperplasia and hypertrophy of VSMC wre determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, [(3)H]-thymidine and [(3)H]-leucine incorporation, and Ca(2+) was measured with Fluo-3/AM staining. Systolic blood pressure (SBP), the ratio of media thickness to lumen diameter (MT/LD) of aorta, collagen content, and phospholipase C activity in aorta were measured in SHR. GCIP-27 (3-100 µg/l) significantly decreased proliferation activity, protein content, incorporation of [(3)H]-thymidine and [(3)H]-leucine, and Ca(2+) level in VSMC. SBP, MT/LD, collagen content, and phospholipase C activity in aorta of SHR were decreased significantly in GCIP-27 (7, 20, 60 µg/kg)-treated groups and losartan (6 mg/kg) group compared with vehicle group. In conclusion, GCIP-27 could inhibit vascular remodeling effectively in vitro and in vivo.
Gq 蛋白位于导致血管重构的信号转导途径的交汇点。Gα 亚基的羧基末端在 G 蛋白-受体相互作用中起着至关重要的作用。本研究旨在探讨合成 Gq 羧基末端模拟肽，即 GCIP-27，对体外血管平滑肌细胞（VSMC）和自发性高血压大鼠（SHR）血管重构的影响。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐（MTT）测定、[(3)H]-胸苷和[(3)H]-亮氨酸掺入以及 Fluo-3/AM 染色测量Ca(2+)来确定 VSMC 的增生和肥大。测量 SHR 的收缩压（SBP）、主动脉中膜厚度与管腔直径的比值（MT/LD）、胶原含量和主动脉中的磷脂酶 C 活性。GCIP-27（3-100 µg/l）显著降低了 VSMC 的增殖活性、蛋白含量、[(3)H]-胸苷和[(3)H]-亮氨酸掺入以及Ca(2+)水平。与对照组相比，GCIP-27（7、20、60 µg/kg）和洛沙坦（6 mg/kg）治疗组 SHR 的 SBP、MT/LD、胶原含量和主动脉中的磷脂酶 C 活性均显著降低。总之，GCIP-27 可有效抑制体外和体内血管重构。
