Modulation of prostaglandin H synthase-2 mRNA expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice.
Modulation of prostaglandin H synthase-2 mRNA expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice.
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2,3,7,8-四氯二苯并-对-二恶英对小鼠前列腺素 H 合酶-2 mRNA 表达的调节。
DOI：
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发表时间：
1998
影响因子：
3.9
通讯作者：
J. Abel
中科院分区：
文献类型：
--
作者：
C. Vogel;U. Schuhmacher;G. Degen;H. Bolt;T. Pineau;J. Abel
前列腺素内过氧化物酶（PGHS-1和PGHS-2）催化前列腺素和血栓烷生物合成的中间步骤。近年来，研究发现2，3，7，8-四氯二苯并对二恶英（TCDD）可调节PGHS-2 mRNA在不同细胞系中的表达。本研究的主要目的是研究是否PGHS-2 mRNA的表达可以改变急性TCDD在体内，第二，我们也有兴趣在是否调制PGHS-2介导的芳香烃受体（AhR），这是已知的参与TCDD诱导的第1和第2相酶的转录控制。最初，C57 BL/6 J小鼠接受10，000 ng TCDD/kg的单次给药，并在肝脏、肺、胸腺、肾脏和脾脏中分析PGHS-1和PGHS-2 mRNA。TCDD对PGHS-1 mRNA的表达无明显影响。TCDD处理后，肺、脾PGHS-2 mRNA表达水平均升高。TCDD对肝脏和肾脏PGHS-2表达无影响。在剂量反应研究中，C57 BL/6 J和DBA/2 J小鼠用不同剂量的TCDD（1- 50，000 ng/kg）处理24小时，并分析肺和脾中PGHS-2 mRNA的增加。在100 ng TCDD/kg剂量下，C57 BL/6 J小鼠肺中PGHS-2 mRNA显著增加，而DBA/2 J小鼠中PGHS-2的增加需要将近100倍的TCDD剂量。在C57 BL/6 J小鼠的脾脏中发现了类似的PGHS-2的剂量依赖性诱导;然而，在DBA/2小鼠的脾脏中未发现PGHS-2的显著增加。这些结果表明AhR参与TCDD介导的PGHS-2表达的变化。这一建议得到了AhR缺陷动物研究的支持，这些研究表明，TCDD对PGHS-2 mRNA没有影响。当PGHS-2的mRNA表达的变化与CYP 1A 1在4和72小时之间的TCDD相比，值得注意的是，TCDD导致延迟和更短暂的增加PGHS-2。这些数据表明，这两个基因的调制机制TCDD可能是不同的。
Prostaglandin endoperoxide H synthases (PGHS-1 and PGHS-2) catalyze an intermediate step in the biosynthesis of prostaglandins and thromboxanes. Recently, it was observed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) modulates the expression of PGHS-2 mRNA in different cell lines. The main aim of this study was to examine whether PGHS-2 mRNA expression can be changed by acute TCDD in vivo and, second, we were also interested in whether modulation of PGHS-2 is mediated by the aryl hydrocarbon receptor (AhR) which is known to be involved in the transcriptional control of TCDD-induced phase 1 and phase 2 enzymes. Initially C57BL/6J mice were treated with a single dose of 10,000 ng TCDD/kg and the PGHS-1 and PGHS-2 mRNAs were analyzed in liver, lung, thymus, kidney, and spleen. In all tissues examined the expression of PGHS-1 mRNA was not affected by TCDD. However, TCDD treatment enhanced the PGHS-2 mRNA levels in lung and spleen. No effect of TCDD on PGHS-2 expression was found in liver and kidney. For dose-response studies C57BL/6J and DBA/2J mice were treated for 24 h with various doses of TCDD (1-50,000 ng/kg) and the PGHS-2 mRNA increases were analyzed in lungs and spleens. A significant increase of PGHS-2 mRNA in lungs of C57BL/6J mice was found at a dose of 100 ng TCDD/kg, whereas a nearly 100-fold higher TCDD dose was needed to increase PGHS-2 in DBA/2J mice. A similar dose-dependent induction of PGHS-2 was found in spleens of C57BL/6J mice; however, no significant increase of PGHS-2 was found in spleens of DBA/2 mice. These results indicate an involvement of AhR in TCDD-mediated changes of PGHS-2 expression. This suggestion is supported by studies in AhR-deficient animals which showed that TCDD had no effect on PGHS-2 mRNA. When changes of PGHS-2 mRNA expression are compared with those of CYP1A1 between 4 and 72 h after TCDD, it is noteworthy that TCDD led to a delayed and more transient increase of PGHS-2. These data suggest that the mechanism of modulation of both genes by TCDD may be different.
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影响因子：
4.7
作者：
Kelley, DJ;Mestre, JR;Dannenberg, AJ
通讯作者：
Dannenberg, AJ
DOI：
10.1073/pnas.93.13.6731
发表时间：
1996-06-25
影响因子：
11.1
作者：
Schmidt, JV;Su, GHT;Bradfield, CA
通讯作者：
Bradfield, CA
影响因子：
4.1
作者：
J. Whitlock
通讯作者：
J. Whitlock
2,3,7,8-四氯二苯并-p-二恶英调节大鼠胸腺细胞中前列腺素 G/H 合酶-2 基因的表达。
DOI：
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发表时间：
1996
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Olnes,MJ;Verma,M;Kurl,RN
通讯作者：
Kurl,RN
前列腺素合成酶抑制剂吲哚美辛对7,12-二甲基苯并(a)蒽诱导的喂食不同脂肪水平的大鼠乳腺肿瘤发生的影响。
影响因子：
11.2
作者：
Carter,CA;Milholland,RJ;Shea,W;Ip,MM
通讯作者：
Ip,MM