Regulation of messenger ribonucleic acid levels for five urea cycle enzymes in cultured rat hepatocytes. Requirements for cyclic adenosine monophosphate, glucocorticoids, and ongoing protein synthesis.
Regulation of messenger ribonucleic acid levels for five urea cycle enzymes in cultured rat hepatocytes. Requirements for cyclic adenosine monophosphate, glucocorticoids, and ongoing protein synthesis.
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DOI：
10.1210/mend-2-5-444
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发表时间：
1988-05
影响因子：
--
通讯作者：
Vicki L. Nebes;Sidney M. Morris
中科院分区：
文献类型：
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作者：
Vicki L. Nebes;Sidney M. Morris
在成年大鼠肝脏中，尿素循环酶的量受饮食、糖皮质激素和cAMP的调节。在化学成分确定的培养基中培养的大鼠肝细胞用于精确定义糖皮质激素和cAMP在翻译前水平调节这些酶的作用。除鸟氨酸转氨甲酰酶mRNA外，培养的大鼠肝细胞保留了表达尿素循环酶mRNA的能力，其表达水平与完整大鼠肝脏相同。在没有添加激素的情况下，乙酰氨基琥珀酸合成酶和乙酰氨基琥珀酸裂解酶的mRNA保持在或高于正常的体内水平，而其他三种酶的mRNA下降到非常低的水平。氨甲酰磷酸合成酶I、氨甲酰琥珀酸合成酶、氨甲酰琥珀酸裂解酶和氨甲酰琥珀酸裂解酶的信使RNA在地塞米松或8-（4-氯苯硫基）cAMP（CPT-cAMP）的作用下增加。半数最大反应发生在2-3 nM地塞米松和2-7 μ M CPT-cAMP。环己酰亚胺取消地塞米松的反应，但不CPT-cAMP，这表明地塞米松诱导表达的中间基因产物诱导这些mRNA所需的。这两种激素的组合的影响是加性的乙酰氨基琥珀酸裂解酶mRNA和氨甲酰磷酸合成酶I，乙酰氨基琥珀酸合成酶，和乙酰氨基琥珀酸酶mRNA的协同作用。鸟氨酸转氨甲酰酶的信使RNA对任何测试条件都几乎没有反应。根据特定的mRNA和激素条件测试，mRNA水平的增加范围从1.4到70倍以上的控制值。（250字处删节）
In adult rat liver, amounts of the urea cycle enzymes are regulated by diet, glucocorticoids, and cAMP. Rat hepatocytes cultured in chemically defined medium were used to precisely define the roles of glucocorticoids and cAMP in regulation of these enzymes at the pretranslational level. With the exception of ornithine transcarbamylase mRNA, cultured rat hepatocytes retain the capacity to express mRNAs for the urea cycle enzymes at the same level observed for liver of intact rats. In the absence of added hormones, mRNAs for argininosuccinate synthetase and argininosuccinate lyase remained at or above normal in vivo levels, while mRNAs for the other three enzymes declined to very low levels. Messenger RNAs for carbamyl phosphate synthetase I, argininosuccinate synthetase, argininosuccinate lyase, and arginase increased in response to either dexamethasone or 8-(4-chlorophenylthio) cAMP (CPT-cAMP). Half-maximal responses occurred at 2-3 nM dexamethasone and at 2-7 microM CPT-cAMP. Cycloheximide abolished the response to dexamethasone but not to CPT-cAMP, suggesting that dexamethasone induced expression of an intermediate gene product required for induction of these mRNAs. The effects of a combination of both hormones were additive for argininosuccinate lyase mRNA and synergistic for carbamyl phosphate synthetase I, argininosuccinate synthetase, and arginase mRNAs. Messenger RNA for ornithine transcarbamylase showed little or no response to any condition tested. Depending on the particular mRNA and hormonal condition tested, increases in mRNA levels ranged from 1.4- to 70-fold above control values.(ABSTRACT TRUNCATED AT 250 WORDS)