Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements.
Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements.
复制标题
小鼠表皮中 3-羟基-3-甲基戊二酰辅酶 A 还原酶活性的调节。
DOI：
10.1172/jci114514
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Feingold,KR
中科院分区：
文献类型：
--
作者：
Proksch,E;Elias,PM;Feingold,KR
表皮胆固醇生物合成受屏障功能调节。我们定量的数量和激活状态（磷酸化去磷酸化）的限速酶，3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶，在表皮屏障破坏之前和之后。在小鼠表皮中，我们发现高酶活性（1.75 +/- 0.02 nmol/min/mg蛋白质）。急性屏障破坏后，酶活性在1.5 h后开始升高，2.5 h时达到最大升高，15 h时恢复正常。慢性屏障破坏增加了83%的总酶活性。在正常表皮中，在NaF-与NaCl-含缓冲液中分离的微粒体中HMG CoA还原酶活性的测量表明，46 +/- 2%的酶处于活性形式。在急性或慢性屏障破坏后，观察到活性形式的HMG CoA还原酶的百分比显著增加。急性中断增加酶的活化状态，早在15分钟，达到最大值后2.5小时，增加仍然存在于15小时，表明激活状态的变化有一个密切的时间关系与屏障功能。总HMG CoA还原酶活性的增加仅发生在深刻的屏障破坏后，而激活状态的变化发生在较低程度的屏障破坏。屏障功能的人工校正阻止了总HMG CoA还原酶活性的增加，并部分阻止了酶活化的增加。这些结果表明屏障需求通过调节HMG CoA还原酶的量和活化状态来调节表皮胆固醇合成。图片
Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl-containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state.Images