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The asparaginyl hydroxylase, factor-inhibiting hypoxia-inducible factor (HIF), is central to the oxygen-sensing pathway that controls the activity of HIF. Factor-inhibiting HIF (FIH) also catalyzes the hydroxylation of a large set of proteins that share a structural motif termed the ankyrin repeat domain (ARD). In vitro studies have defined kinetic properties of FIH with respect to different su...

H ypoparathyroidism is a heterogeneous group of disorders with both acquired and inherited causes, each presenting clinically with hypocalcaemia. Familial cases of hypoparathyroidism may be due to an isolated defect of the parathyroid glands or be a component of a syndrome disorder, examples of which include DiGeorge, hypoparathyroidism-retardation-dysmorphism, and KennyCaffey syndrome. Familia...

PURPOSE Tumor hypoxia is associated with poor prognosis and resistance to treatment. Our aim was to assess the expression of proteins that act as cellular oxygen sensors, directly regulating the hypoxia inducible factor (HIF) pathway, i.e., prolyl hydroxylase domain proteins (PHD)-1, PHD-2, PHD-3, and FIH in pancreatic endocrine tumors (PET). EXPERIMENTAL DESIGN Immunohistochemical expression...

BACKGROUND Under normoxic conditions, hypoxia-inducible factor (HIF)-1α is rapidly degraded by 2 hydroxylases: prolyl hydroxylase (PHD) and factor-inhibiting HIF-1 (FIH). Because HIF-1α mediates the cardioprotective response to ischemic injury, its upregulation may be an effective therapeutic option for ischemic heart failure. METHODS AND RESULTS PHD and FIH were cloned from mouse embryonic s...

H ypoparathyroidism is a heterogeneous group of disorders with both acquired and inherited causes, each presenting clinically with hypocalcaemia. Familial cases of hypoparathyroidism may be due to an isolated defect of the parathyroid glands or be a component of a syndrome disorder, examples of which include DiGeorge, hypoparathyroidism-retardation-dysmorphism, and KennyCaffey syndrome. Familia...

The HIF (hypoxia-inducible factor) plays a central regulatory role in oxygen homoeostasis. HIF proteins are regulated by three Fe(II)- and α-KG (α-ketoglutarate)-dependent prolyl hydroxylase enzymes [PHD (prolyl hydroxylase domain) isoenzymes 1-3 or PHD1, PHD2 and PHD3] and one asparaginyl hydroxylase [FIH (factor inhibiting HIF)]. The prolyl hydroxylases control the abundance of HIF through ox...

Although nickel and cobalt compounds have been known to cause induction of the transcription factor hypoxia-inducible factor 1 (HIF-1) and activation of a battery of hypoxia-inducible genes in the cell, the molecular mechanisms of this induction remain unclear. The post-translational modification of HIF-1a, the oxygen-sensitive subunit of HIF-1, regulates stabilization, nuclear translocation, D...

Amphotericin B (AmB) is widely used for treating severe systemic fungal infections. However, long-term AmB treatment is invariably associated with adverse effects such as anemia. The erythropoietin (EPO) suppression by AmB has been proposed to contribute to the development of anemia. However, the mechanism whereby EPO is suppressed remains obscure. In this study, we investigated the possibility...

Aspartyl-(Asparginyl)-β-Hydroxylase (AAH) promotes cell motility by hydroxylating Notch. Insulin and insulin-like growth factor, type 1 (IGF-I) stimulate AAH through Erk MAPK and phosphoinositol-3-kinase-Akt (PI3K-Akt). However, hypoxia/oxidative stress may also regulate AAH. Hypoxia inducible factor-1 alpha (HIF-1α) regulates cell migration, signals through Notch, and is regulated by hypoxia/o...