Current Pharmaceutical Design - Volume 15, Issue 33, 2009

Within the last decade it became evident that a family of hypoxia-inducible transcription factors (HIFs) are key players in the cellular response to limited O2 supply. From the three HIFs known today, HIF-1 is the best characterized and it appears to be of special interest since it activates transcription of glycolytic enzymes and glucose transporters as well as angiogenic growth factors to improve nutrient and blood supply t Read More

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1α and HIF-1α subunits, which is activated in response to reduced O2 availability. HIF-1 transactivates genes encoding proteins that are involved in key aspects of the cancer phenotype, including cell immortalization and de-differentiation, stem cell maintenance, genetic instability, glucose uptake and metabolism, pH regulation, autocrine growth/survi Read More

The hypoxia-inducible factor HIF-1 has been shown to be mandatory for the cellular adaptation to hypoxia. In addition, evidence has been provided that HIF-1 can mediate various stress responses and that it may play an important role under inflammatory conditions even independently of hypoxia. HIF-1 is a heterodimer consisting of an α-subunit which is subject to tight regulation, and a β-subunit, also termed ARNT, which Read More

The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1β subunit is constitutively expressed, but the levels of the HIF-1α subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1α production and degradation. While the regula Read More

Recent studies have established that the regulation of microRNAs (miRs) is a feature of the hypoxic response. In this review, we discuss the role of hypoxia-regulated miRs, with an emphasis on miR-210 and miR-373, and anticipate directions for clinical applications. The induction of miR-210 and miR-373 is dependent upon hypoxia inducible factor (HIF), and their up-regulation has been detected in a variety of solid tumors. Both m Read More

The hypoxia-inducible factor-1 (HIF-1) is a key regulator in the mammalian response to oxygen deficiency under both physiological and pathological conditions such as cancer. A number of studies indicated an association between tumor hypoxia, increased hypoxia-inducible factor (HIF-1α) levels and a poor prognosis. The HIF-1α regulation in response to hypoxia occurs primarily on the level of protein stability due to posttranslatio Read More

Hypoxia-inducible transcription factor (HIF) is the master regulator of hypoxia-inducible genes involved in the mediation of survival and adaptive responses to insufficient oxygen availability, such as genes involved in hematopoesis, angiogenesis, iron transport, glucose utilization, resistance to oxidative stress, cell proliferation, survival and apoptosis, extracellular matrix homeostasis, and tumor progression. The stability of the H Read More

Protein stability of hypoxia-inducible factor (HIF) α subunits is regulated by the oxygen-sensing prolyl-4- hydroxylase domain (PHD) enzymes. Under oxygen-limited conditions, HIFα subunits are stabilized and form active HIF transcription factors that induce a large number of genes involved in adaptation to hypoxic conditions with physiological implications for erythropoiesis, angiogenesis, cardiovascular function and cellular me Read More

Hypoxia-inducible factors (HIFs) are heterodimeric oxygen-sensitive basic helix-loop-helix transcription factors that play central roles in cellular adaptation to low oxygen environments. The von Hippel-Lindau tumor suppressor (pVHL) is the substrate recognition component of an E3 ubiquitin ligase and functions as a master regulator of HIF activity by targeting the hydroxylated HIF-alpha subunit for ubiquitylation and rapid pro Read More

Cellular and systemic oxygen homeostasis is regulated by an oxygen-sensitive signalling pathway centred on a transcription factor known as Hypoxia Inducible Factor (HIF). Regulation of HIF activity and protein stability is mediated by a family of hydroxylases that act as oxygen sensors due to the dependence of the hydroxylation reaction on oxygen. The transcriptional activity of HIF is at least in part determined by aspa Read More

Stem cell based therapies for cerebral ischemia (CI) utilize different cell sources including embryonic stem cells (ESCs), neural stem cells (NSCs), umbilical cord blood cells (UCBCs), mesenchymal stem cells (MSCs), and some immortalized cell lines. To date, experimental studies showed that all of these cell sources have been successful to some extent in attenuating the ischemic damage and improving functional recovery after Read More