Hypoxia response

HIF as master regulator of hypoxia responsive gene expression... 

Oosthuyse, B., Moons, L., Storkebaum, E. et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promotor causes motor neuron degeneration. Nat. Genet. 28 131-138, 2001. 

Recent studies have demonstrated that overexpression of HDACl represses the tumor suppressors, p53 and von Hippel-Lindau (VHL), but induces the hypoxia-responsive genes, hypoxia inducible factor alpha (HIF-la) and vascular endothelial growth factor (VEGF) and increases angiogenesis. Conversely, HDAC inhibitors derepress the tumor suppressors, p53 and VHL, and repress HIF-la and VEGF [68, 69]. 

Responses to low oxygen tension in tissues (hypoxia) are important to all aerobic organisms.464/467a d In mammals transcription of hypoxia-responsive genes is regulated by hypoxia inducible factors HIF-1 and... 

Blancher, C. and Harris, A.L. (1998) The molecular basis of the hypoxia response pathway tumour hypoxia as a therapy target. Cancer Metastasis Rev., 17, 187-194. 

Shibata, T., Giaccia, A. J. and Brown, J.M. (2000) Development of a hypoxia-responsive vector for tumor-specific gene therapy. Gene Then, 7, 493 198. 

It is perhaps not surprising that these studies also detected the induction of genes involved in signaling and coordination of hypoxia-responsive physiological processes. For example, ele-... 

Semenza, G.L., B. Jiang, S.W. Leung, R. Passantino, J. Concordet, P. Maire, and A. Giallongo (1996). Hypoxia response elements in the aldolase A, eno-lase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia Inducible Factor-1. J. Biol. Chem. 271 32529-32537. 

Figure 5.1. The interplay between time and adaptational options occurs in human as well as in animal evolution of physiological systems. The acute and acclimation effects on human hypoxia response physiology can be readily evaluated. However, adaptations requiring generations of time of course cannot be studied by direct manipulations in humans. All workers in this area therefore rely upon comparing human lineages adapted to hypobaric hypoxia in different regions of the world and for different time periods. Two such groups that have extensively studied in this manner are Quechuas and Aymaras from the Andes, and Sherpas and Tibetans from the Himalayas. See chapter 1 for further discussion of time and adaptation options.

Acute high-altitude studies of both human and animal models indicate that hypoxia defenses are initiated by several oxygen sensing, signal transduction pathways. For convenience, these have been summarized as five general hypoxia response systems (figure 5.2(A)-(E) ... 

Oxygen-Sensor-Mediated Hypoxia Response Systems... 

Not All Hypoxia Response Systems in Indigenous High-Altitude People Are Exactly the Same... 

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