Hypoxia in vivo decreases peroxisome proliferator-activated receptor α-regulated gene expression in rat heart
Hypoxia in vivo decreases peroxisome proliferator-activated receptor α-regulated gene expression in rat heart
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DOI：
10.1006/bbrc.2001.5541
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发表时间：
2001-09-14
影响因子：
3.1
通讯作者：
Taegtmeyer, H
中科院分区：
文献类型：
--
作者：
Razeghi, P;Young, ME;Taegtmeyer, H
我们测试了以下假设：缺氧会降低体内心肌中 PPAR α 调节的基因表达。在两种全身性缺氧大鼠模型（氯化钴治疗和等容血液稀释）中，使用实时测量 PPARα 和 PPARa 调节基因（丙酮酸脱氢酶激酶 4 (PDK4)、肌肉肉毒碱棕榈酰转移酶-I (mCPT-I) 和丙二酰辅酶 A 脱羧酶 (MCD)）的转录水平 定量RT-PCR。数据针对管家基因β-肌动蛋白进行标准化。不受 PPARa 调节的心房钠尿因子 (ANF) 和丙酮酸脱氢酶激酶 2 (PDK2) 作为对照。 CoCl2 治疗降低了 PPARa、PDK4、mCPT-I 和 MCD mRNA 水平。等容性贫血还导致 PPARa、PDK4 和 MCD mRNA 水平显着下降。 mCPT-I 的转录水平略有下降，但不显着（P = 0.08）。 β-肌动蛋白、APM 和 PDK2 的基因表达不会因 CoCl2 治疗或贫血而改变。在两种体内缺氧模型中，心肌 PPARa 调节的基因表达降低。这些结果表明缺氧期间减少脂肪氧化和增加心脏对葡萄糖的依赖的转录机制。 (C) 2001 年学术出版社。
We tested the hypothesis that hypoxia decreases PPAR alpha -regulated gene expression in heart muscle in vivo. In two rat models of systemic hypoxia (cobalt chloride treatment and iso-volemic hemodilution), transcript levels of PPAR alpha and PPARa-regulated genes (pyruvate dehydrogenase kinase 4 (PDK4), muscle carnitine palmitoyltransferase-I (mCPT-I), and malonyl-CoA decarboxylase (MCD)) were measured using real-time quantitative RT-PCR. Data were normalized to the housekeeping gene beta -actin. Atrial natriuretic factor (ANF) and pyruvate dehydrogenase kinase 2 (PDK2), which are not regulated by PPARa, served as controls. CoCl2 treatment decreased PPARa, PDK4, mCPT-I, and MCD mRNA levels. Iso-volemic anemia also caused a significant decrease in PPARa, PDK4, and MCD mRNA levels. Transcript levels of mCPT-I showed a slight, but not significant decrease (P = 0.08). Gene expression of beta -actin, APM, and PDK2 did not change with either CoCl2 treatment nor with anemia. Myocardial PPARa-regulated gene expression is decreased in two models of hypoxia in vivo. These results suggest a transcriptional mechanism for decreased fatty oxidation and increased reliance of the heart for glucose during hypoxia. (C) 2001 Academic Press.