Catron T, Mendiola M A, Smith S M, Born J, Walker M K
College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA.
Biochem Biophys Res Commun. 2001 Mar 30;282(2):602-7. doi: 10.1006/bbrc.2001.4613.
The aryl hydrocarbon receptor nuclear translocator (Arnt) and hypoxia-inducible factor (HIF)-1alpha mediate cellular responses to hypoxia. We investigated the ability of hypoxia to regulate Arnt and HIF-1alpha mRNA in the heart in vivo. We cloned avian Arnt, developed an in vivo model of chronic cardiac hypoxia, and measured expression of cardiac Arnt and HIF-1alpha mRNA by quantitative RT-PCR. Chronic hypoxic exposure (24 h to 15% O(2)) of day 9 chick embryos resulted in a 30-fold increase in covalent binding of (3)H-misonidazole, a hypoxic tissue marker, to cardiac tissue, and a 2-fold induction of cardiac inducible nitric oxide synthase mRNA, compared to normoxic controls. In this same model, cardiac Arnt mRNA expression decreased by 35%, while HIF-1alpha mRNA expression increased 400%. These data suggest that regulation of Arnt and HIF-1alpha mRNA expression may contribute to the physiological responses of the heart during prolonged hypoxia.
芳烃受体核转运蛋白(Arnt)和缺氧诱导因子(HIF)-1α介导细胞对缺氧的反应。我们研究了缺氧在体内调节心脏中Arnt和HIF-1α mRNA的能力。我们克隆了禽类Arnt,建立了慢性心脏缺氧的体内模型,并通过定量逆转录聚合酶链反应测量心脏中Arnt和HIF-1α mRNA的表达。与常氧对照组相比,第9天鸡胚经24小时至15% O₂的慢性低氧暴露后,缺氧组织标志物³H-米索硝唑与心脏组织的共价结合增加了30倍,心脏诱导型一氧化氮合酶mRNA诱导增加了2倍。在同一模型中,心脏Arnt mRNA表达下降了35%,而HIF-1α mRNA表达增加了400%。这些数据表明,Arnt和HIF-1α mRNA表达的调节可能有助于心脏在长期缺氧期间的生理反应。