Hayashi A, Suzuki T, Wachi H, Tajima S, Nishikawa T, Murad S, Pinnell S R
Department of Dermatology, Keio University School of Medicine, Shinjuku, Japan.
Arch Biochem Biophys. 1994 Nov 15;315(1):137-41. doi: 10.1006/abbi.1994.1482.
Minoxidil was found to inhibit the proliferation of smooth muscle cells in the proliferating phase, but not in the quiescent phase. Treatment of proliferating or quiescent cells with minoxidil resulted in a dose- and time-dependent stimulation of elastin synthesis specifically. Maximum stimulation (fourfold) occurred in cells treated with 1 mM minoxidil for 48 h. The stimulation of elastin synthesis was accompanied by a proportional increase in elastin mRNA level, and it was partially prevented by a K+ channel blocker (tetraethylammonium) and completely prevented by high K+ salt (0.1 M). Minoxidil had no significant effect on the extent of prolyl hydroxylation in newly synthesized elastin. These results indicate that minoxidil stimulates elastin synthesis at a pretranslational level by a mechanism unrelated to cell proliferation but one that may involve K+ efflux. As a pharmacological agent capable of stimulating elastin expression, minoxidil would be a useful drug for the treatment of abnormal elastin metabolism.
发现米诺地尔可抑制增殖期平滑肌细胞的增殖,但对静止期细胞无此作用。用米诺地尔处理增殖期或静止期细胞,会特异性地导致弹性蛋白合成呈剂量和时间依赖性刺激。在用1 mM米诺地尔处理48小时的细胞中出现最大刺激(四倍)。弹性蛋白合成的刺激伴随着弹性蛋白mRNA水平的成比例增加,并且部分被钾通道阻滞剂(四乙铵)阻断,完全被高钾盐(0.1 M)阻断。米诺地尔对新合成弹性蛋白中的脯氨酰羟化程度无显著影响。这些结果表明,米诺地尔通过一种与细胞增殖无关但可能涉及钾外流的机制,在翻译前水平刺激弹性蛋白合成。作为一种能够刺激弹性蛋白表达的药物,米诺地尔将是治疗弹性蛋白代谢异常的有用药物。