1. Matt Macoul BMCB 658 4/6/2012

2. Effects of High Altitudes  Low oxygen pressure Hypoxia  Not just from altitude Heart Attack Stroke  Affects cellular respiration and more

3. The Body’s Response  Increase in red blood cells Erythropoietin (EPO)  Formation of new capillaries Vascular Endothelial Growth Factor (VEGF)

4. Hypoxia Inducible Factors (HIFs)  Hypoxia Inducible Factors (HIFs)  Heterodimeric form HIFα HIFβ  Many possible triggers

6. Summary O2 available Normoxia Binds to pVHL Forms complex Hydroxylated HIF Unable to upregulate Growth limited Degrades O2 unavailable Hypoxia Stabilizes Forms dimers Accumulation Increases EPO, VEGF, etc. Upregulates

7. Applications & Possibilities  Tumors Inhibition of HIF may inhibit tumor growth  Anemia Activation of HIF may help complications of disease

8. References Hsieh MM, Linde NS, Wynter A, Metzger M, Wong C, et al. (2007) HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques. In Blood. 2007;110:2140–2147 Jensen, R., Ragel, B., Whang, K., & Gillespie, D. (2006). Inhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas. In Journal Of Neuro-Oncology, 78(3), 233-247 Peet, D., Hampton-Smith, R. (2007) Hypoxia-inducible factor. In AccessScience. Retrieved from http://www.accessscience.com.libproxy.unh.edu/content.aspx?searchStr=hif&id=YB071150