Pinnell S R, Murad S
Department of Medicine, Duke University Medical Center, Durham, N.C.
Dermatologica. 1987;175 Suppl 2:12-8. doi: 10.1159/000248891.
Two important findings related to the effect of minoxidil on human skin fibroblasts in culture are reviewed. Treatment of cells with minoxidil is associated with a specific loss of lysyl hydroxylase activity; this loss occurs gradually and is reversed by removing minoxidil from the culture medium. Experiments with inhibitors of protein and RNA synthesis reveal that minoxidil may inhibit the synthesis of lysyl hydroxylase by acting at the transcriptional level. Treatment of cells with minoxidil is also associated with inhibition of proliferation, without any sign of cytotoxicity. This effect of minoxidil is accompanied by inhibition of DNA synthesis. Since collagen is the major product of fibroblast activity and lysyl hydroxylase catalyzes a crucial reaction in collagen biosynthesis, the combined effects of minoxidil offer the potential for its use as an antifibrotic agent. Thus, minoxidil may prove to be beneficial in treating skin conditions associated with collagen accumulation.
本文综述了与米诺地尔对培养的人皮肤成纤维细胞作用相关的两项重要发现。用米诺地尔处理细胞会导致赖氨酰羟化酶活性特异性丧失;这种丧失是逐渐发生的,并且通过从培养基中去除米诺地尔可以逆转。蛋白质和RNA合成抑制剂实验表明,米诺地尔可能通过在转录水平起作用来抑制赖氨酰羟化酶的合成。用米诺地尔处理细胞还会导致增殖受到抑制,且没有任何细胞毒性迹象。米诺地尔的这种作用伴随着DNA合成的抑制。由于胶原蛋白是成纤维细胞活性的主要产物,而赖氨酰羟化酶催化胶原蛋白生物合成中的关键反应,米诺地尔的综合作用使其具有用作抗纤维化药物的潜力。因此,米诺地尔可能被证明对治疗与胶原蛋白积累相关的皮肤疾病有益。