Transcriptional regulation of α1-adrenoceptor gene in the rat liver during different phases of sepsis
Transcriptional regulation of α1-adrenoceptor gene in the rat liver during different phases of sepsis
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DOI：
10.1016/s0925-4439(98)00102-1
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发表时间：
1999-02-24
影响因子：
6.2
通讯作者：
Liu, MS
中科院分区：
文献类型：
--
作者：
Dong, LW;Yang, J;Liu, MS
本文研究了脓毒症不同时期大鼠肝脏α 1肾上腺素能受体（α 1 AR）基因表达的变化。通过盲肠结扎穿孔（CLP）诱导脓毒症。脓毒症大鼠表现出两个不同的代谢阶段：初始高血糖阶段（CLP后9小时，早期脓毒症），随后是低血糖阶段（CLP后18小时，晚期脓毒症）。[H-3]哌唑嗪结合研究表明，α（1）AR的密度在脓毒症早期增加了30%，而在脓毒症晚期减少了24%。蛋白质印迹分析显示，α（1）AR蛋白水平在早期脓毒症中升高了48%，但在晚期脓毒症中降低了55%。北方印迹分析显示，脓毒症早期α（1b）AR mRNA的稳态水平增加了21%，但在脓毒症晚期下降了29%。细胞核流出实验表明，脓毒症早期α（1b）AR基因转录本的转录率增加76%，而晚期则下降29%。放线菌素D脉冲追踪研究表明，在脓毒症的早期和晚期，α（1b）AR mRNA的半衰期保持不变。这些结果表明，在脓毒症早期，α（1b）AR基因转录速率的增加与α（1b）AR mRNA丰度和α（1）AR蛋白水平的升高相一致，而在脓毒症晚期，α（1b）AR基因转录速率的降低与α（1b）AR mRNA丰度的降低和α（1）大鼠肝脏中AR蛋白水平。这些观察结果表明，在脓毒症进展过程中，大鼠肝脏中α（1）AR基因的表达改变受到转录调控。(C)1999 Elsevier Science B. V.保留所有权利。
Changes in alpha(1)-adrenoceptor (alpha(1)AR) gene expression in the rat liver during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hyperglycemic phase (9 h after CLP, early sepsis) followed by a hypoglycemic phase (18 h after CLP; late sepsis). The [H-3]prazosin binding studies show that the density of alpha(1)AR was increased by 30% during the early phase while it was decreased by 24% during the late phase of sepsis. Western blot analyses reveal that alpha(1)AR protein level was elevated by 48% during early sepsis but was decreased by 55% during late sepsis. Northern blot analyses depict that the steady-state level of alpha(1b)AR mRNA was enhanced by 21% during the early phase but was declined by 29% during the late phase of sepsis. Nuclear run-off assays show that the transcription rate of alpha(1b)AR gene transcript was increased by 76% during early sepsis while it was decreased by 29% during late sepsis. The actinomycin D pulse-chase studies indicate that the half-life of alpha(1b)AR mRNA remained unaffected during the early and the late phases of sepsis. These findings demonstrate that during the early phase of sepsis, the increase in the rate of transcription of alpha(1b)AR gene paralleled with the elevations in the alpha(1b)AR mRNA abundance and alpha(1)AR protein level, while during the late phase of sepsis, the decrease in the rate of transcription of alpha(1b)AR gene coincided with the declines in the alpha(1b)AR mRNA abundance and the alpha(1)AR protein level in the rat liver. These observations indicate that the altered expression of alpha(1)AR genes in the rat liver during the progression of sepsis was regulated transcriptionally. (C) 1999 Elsevier Science B.V. All rights reserved.