Hydralazine differentially increases mRNAs for the alpha and beta subunits of prolyl 4-hydroxylase whereas it decreases pro alpha 1(I) collagen mRNAs in human skin fibroblasts.
Hydralazine differentially increases mRNAs for the alpha and beta subunits of prolyl 4-hydroxylase whereas it decreases pro alpha 1(I) collagen mRNAs in human skin fibroblasts.
复制标题
肼屈嗪会差异性地增加脯氨酰 4-羟化酶 α 和 β 亚基的 mRNA，而降低人皮肤成纤维细胞中的前 α 1(I) 胶原蛋白 mRNA。
DOI：
10.1016/0003-9861(91)90430-q
复制
发表时间：
1991
影响因子：
3.9
通讯作者：
Pinnell,SR
中科院分区：
文献类型：
--
作者：
Yeowell,HN;Murad,S;Pinnell,SR
We have used specific oligonucleotide probes to measure the effect of hydralazine on mRNA levels of the α and β subunits of prolyl 4-hydroxylase (PH), a key post-translational modifying enzyme in collagen biosynthesis. Hydralazine exerts a paradoxical effect on collagen biosynthesis in cultured fibroblasts. Cells exposed to hydralazine synthesize substantially reduced amounts of collagen, which is severely deficient in hydroxyproline. Surprisingly, however, the level of prolyl hydroxylase activity assayed in extracts of treated cells is markedly increased, suggesting overproduction of the enzyme. Hybridization analysis indicated that in untreated cells the concentration of the αPH subunit mRNA was about 20–25% of the βPH subunit mRNA concentration. Hydralazine treatment increased the mRNAs for both α and β subunits of PH by three- to fourfold. A differential induction of these mRNAs was observed, however. The α subunit mRNA was maximally increased within 24 h, whereas the β subunit mRNA was increased more slowly, reaching a maximum at 72 h. In contrast, the 5.8 and 4.8-kb mRNAs for proα1(I) collagen were virtually eliminated by 72 h. This study demonstrates that the increased prolyl hydroxylase activity is a direct result of hydralazine-mediated increases in steady state mRNA content for the α and β subunits of this enzyme. Moreover, the earlier induction of αPH mRNA may provide the first evidence at the mRNA level that regulation of PH activity occurs mainly through regulation of the α subunit of PH. In addition, the decrease in collagen synthesis by hydralazine appears to result directly from suppression of both species of mRNA for proα1(I) collagen.
