Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression
Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression
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DOI：
10.1073/pnas.93.18.9443
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Ntambi, JM
中科院分区：
文献类型：
--
作者：
Miller, CW;Ntambi, JM
过氧化物酶体增殖剂诱导肝脏中的硬脂酰辅酶A去饱和酶活性（EC 1.14.99.5）[Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim.生物物理学。 Acta 752, 259-264]。我们分析了硬脂酰辅酶A去饱和酶1 (SCD1) mRNA的变化，以进一步明确过氧化物酶体增殖剂诱导硬脂酰辅酶A去饱和酶的分子机制。对喂食添加了安妥明或吉非贝齐的饮食的 BALB/c 小鼠的肝脏中的 SCD1 mRNA 进行了分析。发现氯贝特可在 6 小时内诱导肝脏 SCD1 mRNA 水平增加 3 倍，在 30 小时内最多增加 22 倍。吉非罗齐给药导致类似的诱导模式。这种诱导主要是由于 SCD1 基因转录的增加，如转染的 SCD1-氯霉素乙酰转移酶融合基因的核连续转录测定和 DNA 缺失分析所示。过氧化物酶体增殖物激活受体 (PPAR) 的顺式连接反应元件定位于 SCD1 启动子碱基对 -664 至 -642 之间的 AGGTCA 共有序列。氯贝特介导的 SCD1 mRNA 诱导被证明与多不饱和脂肪酸无关，过氧化物酶体增殖剂和花生四烯酸对 SCD1 mRNA 水平具有相反的影响。此外，安妥明对 SCD1 mRNA 的激活被放线菌酮抑制了 77%。这些饮食控制没有改变肝脏 β-肌动蛋白和白蛋白 mRNA 的水平。我们的数据表明，肝脏 SCD1 基因表达受 PPAR 调节，并表明过氧化物酶体增殖剂和多不饱和脂肪酸通过不同的机制发挥作用。
Peroxisome proliferators induce stearoyl-CoA desaturase activity (EC 1.14.99.5) in liver [Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim. Biophys. Acta 752, 259-264]. We analyzed the changes in stearoyl-CoA desaturase 1 (SCD1) mRNA to further define the molecular mechanism for the induction of stearoyl-CoA desaturase by peroxisome proliferators. SCD1 mRNA was analyzed from the livers of BALB/c mice that had been fed diets supplemented with clofibrate or gemfibrozil. Clofibrate was found to induce liver SCD1 mRNA levels 3-fold within 6 hr to a maximum of 22-fold in 30 hr. Gemfibrozil administration resulted in a similar induction pattern. This induction is primarily due to an increase in transcription of the SCD1 gene, as shown by nuclear run-on transcription assays and DNA deletion analysis of transfected SCD1-chloramphenicol acetyltransferase fusion genes. The cis-linked response element for peroxisome proliferator-activated receptor (PPAR) was localized to an AGGTCA consensus sequence between base pairs -664 to -642 of the SCD1 promoter. Clofibrate-mediated induction of SCD1 mRNA was shown to be independent of polyunsaturated fatty acids, with peroxisome proliferators and arachidonic acid having opposite effects on SCD1 mRNA levels. Additionally, the activation of SCD1 mRNA by clofibrate was inhibited 77% by cycloheximide administration. Levels of liver beta-actin and albumin mRNAs were unchanged by these dietary manipulations. Our data show that hepatic SCD1 gene expression is regulated by PPARs and suggest that peroxisome proliferators and polyunsaturated fatty acids act through distinct mechanisms.