Hypoxic response elements

Figure 1 Role of prolyl hydroxylases as an oxygen-sensor regulating HIF activation. In the presence of oxygen, PHD enzymes convert specific prolyl residues in HIF-a chains to hydroxyproline. The enzymes require iron as a cofactor. Modified HIF-a chains are captured hy the pVHL ubiquitin E3 ligase complex, ubiquitylated, and destroyed by the proteasome. Under reduced oxygenation, HIF-a rapidly accumulates, enters the nucleus, dimerizes with a jS subunit, recruits coactivators, and activates transcription of genes with hypoxic response elements (HRE). HYP, hydroxyproline.

M. R. Olive, W. J. Peacock, E. S. Dennis (1991) The anaerobic responsive element contains two GC-rich sequences essential for binding a nuclear protein and hypoxic activation of the maize adhl promoter. Nucl. Acids Res., 19 7053-7960... 

Firth, J.D., B.L. Ebert, and P.J. Ratcliffe (1995). Hypoxic regulatin of LDH A interaction betwee hypoxia inducible factor 1 and cAMP response elements. J. Biol. Chem. 270 21021-21027. 

Delivery of gene transfer systems of heat shock proteins (Hsp70),250 antioxidant enzymes (catalase)251 or survival genes (Akt)252 has been associated with myocardial protection against ischemia and reperfusion. A vector gene therapy system has also been developed with a hypoxia response element-incorporated promoter to turn on the gene expression in response to hypoxic signal.253... 

Firth JD, Ebert BL, Ratcliffe PJ. 1995. Hypoxic regulation of lactate dehydrogenase A Interaction between hypoxia-inducible ftictor 1 and cAMP response elements. J Biol Chem 270 21021-21027. 

Jiang, Y., Vasconcelles, M.J., Wretzel, S., Light, A., Martin, C.E. and Goldberg, M.A. MGA2 is involved in the low-oxygen response element-dependent hypoxic induction of genes in Saccharomyces cerevisiae. Mol Cell Biol, 21 (2001) 6161-6169. 

Tuttolomondo A, Di Raimondo D, di Sciacca R, Pinto A, Licata G (2008) Inflammatory cytokines in acute ischemic stroke. CurrPharm Des 14 3574-3589 van Wijk SJ, Haegeman GJ (2005) Poly(ADP-ribose) polymeiase-1 mediated caspase-independent cell death after ischemia/reperfusion. Free Rad Biol Med 39 81-90 Walton M, Siiimanne E, Williams C, Gluckman P, Dragunow M (1996) The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair. Brain Res Mol Brain Res 43 21-29... 

Vasconcelles MJ, Jiang Y, McDaid K, Gilooly L, Wretzel S, Porter DL. Identification and characterization of a low oxygen response element involved in the hypoxic induction of a family of Saccharomyces cerevisiae genes. J Biol Chem 2001 276 14374-14384. 

Blanchard KL, Acquaviva AM, Galson DL, Bunn HF Hypoxic induction of the human erythropoietin gene cooperation between the promoter and enhancer, each of which contains steroid receptor response elements. Mol Cell Biol 1992 12(12) 5373-5385. 

The molecular machinery involved in the transduction of the hypoxic stimulus into a neurosecretory response in chemoreceptor cells of the carotid body (CB) is not completely known, but current models (e.g., 23,24,27) include the minimal molecular steps and molecular elements shown in the Table 1. 

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