Déry Marc-André C, Michaud Maude D, Richard Darren E
Centre de recherche de L'Hôtel-Dieu de Québec, Department of Medicine, Université Laval, 10 Rue McMahon, Qué., Canada G1R 2J6.
Int J Biochem Cell Biol. 2005 Mar;37(3):535-40. doi: 10.1016/j.biocel.2004.08.012.
Oxygen availability is crucial for cellular metabolism. Hypoxia-inducible factor 1 (HIF-1) is the major oxygen homeostasis regulator. Under normoxic conditions, HIF-1 is rapidly degraded by the proteasome. However, under hypoxic conditions, HIF-1 is stabilized and permits the activation of genes essential to cellular adaptation to low oxygen conditions. These genes include the vascular endothelial growth factor (VEGF), erythropoietin and glucose transporter-1. There is increasing evidence showing that HIF-1 is also implicated in biological functions requiring its activation under normoxic conditions. Amongst others, growth factors and vascular hormones are implicated in this normoxic activation. In this review, we will focus on differences between hypoxic and non-hypoxic induction and activation of HIF-1. We will also discuss the biological functions of HIF-1 associated with these two induction pathways. The clear understanding of both HIF-1 activation mechanisms could have a major impact in cancer and vascular disease.
氧的可利用性对细胞代谢至关重要。缺氧诱导因子1（HIF-1）是主要的氧稳态调节因子。在常氧条件下，HIF-1被蛋白酶体迅速降解。然而，在缺氧条件下，HIF-1会被稳定下来，并允许激活细胞适应低氧条件所必需的基因。这些基因包括血管内皮生长因子（VEGF）、促红细胞生成素和葡萄糖转运蛋白-1。越来越多的证据表明，HIF-1也参与了在常氧条件下需要其激活的生物学功能。其中，生长因子和血管激素与这种常氧激活有关。在这篇综述中，我们将重点关注缺氧和非缺氧诱导及激活HIF-1之间的差异。我们还将讨论与这两种诱导途径相关的HIF-1的生物学功能。对HIF-1两种激活机制的清晰理解可能会对癌症和血管疾病产生重大影响。
