Matt Macoul BMCB 658 4/6/2012. Effects of High Altitudes  Low oxygen pressure Hypoxia  Not just from altitude Heart Attack Stroke  Affects cellular.

Slides:



Advertisements
Similar presentations
Von Hippel-Lindau Syndrome (VHL) Presented by Kelley Montoya March 20, 2003.
Advertisements

Preeclampsia - Hypertension & proteinuria in last trimester of pregnancy - Complicates 2-3 % pregnancies - Requires placenta (even if no fetus; hydatidiform.
TYPES OF HYPOXIA AIDELOMON, EMMANUEL. WHAT IS HYPOXIA? Hypoxia is a pathological condition in which the body as a whole (generalized hypoxia) or a region.
INTRODUCTION Both Type I and Type II diabetes are characterized by increased circulating levels of glucose (hyperglycemia). A major complication of chronic.
Hypoxia Inducible Factor – 1 (HIF-1): A High Impact Factor Free Radical & Radiation Biology College of Medicine The University of Iowa
BME- Short Presentation SHANTE DEZRICK 11/7/12. Common denominator in most common diseases. New capillary blood vessel growth in the body. Natural process.
The Function of VHL and pVHL Protein VHL is a tumor suppressor gene on chromosome 3 Helps to regulate and destroy the alpha subunit of hypoxia-inducible.
PVHL and von Hippel-Lindau Disease Tanner Fadero BIOL 445 April 14, 2015.
Hemoglobin concentration and reproductive fitness of Tibetan women in highland Nepal Cynthia M Beall, Ph.D. Case Western Reserve University Geoff Childs,
Pavel Yarmolenko Biology 169, Spring 2005 The von Hippel-Lindau (VHL) Tumor Suppressor Gene Inactivation and Its Involvement in Tumorgenesis.
The tumor microenvironment: problems and opportunities for therapy Nic Denko PhD MD Radiobiology 2013.
Intermittent hypoxic training. Intermittent hypoxic training (or therapy) (IHT) is a non-invasive, drug-free technique aiming to improve human performance.
Scavenger Hunt Circulatory System. Takes blood away from the heart. heart.
Erythropoietin (EPO) Essentials Erin Drumheller, BSN SRNA York College of Pennsylvania.
Von Hippel-Lindau Syndrome
Targeting HIF2α in Clear-Cell Renal Cell Carcinoma
Angiogenesis and hepatocellular carcinoma
Volume 76, Issue 9, Pages (November 2009)
HIF1a Pathway ProteinLounge.com Glucose Glucose Glucose Transporter
Locatelli et al. Am J Nephrol 2017;45:   (DOI: / )
Nat. Rev. Nephrol. doi: /nrneph
HIFs: a-cute answer to inflammation?
Prolyl‐hydroxylase‐domain proteins regulate hypoxia inducible factor‐α in response to O2 availability. Prolyl‐hydroxylase‐domain proteins regulate hypoxia.
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD  Nupur Gupta, MD, Jay B. Wish, MD  American.
Inducing Angiogenesis
Louise E. Glover, Sean P. Colgan  Gastroenterology 
Toshio Miyata, Norio Suzuki, Charles van Ypersele de Strihou 
Pocket-sized iron regulators: one size fits all?
von Hippel-Lindau Disease
Silencing of eIF3e promotes blood perfusion recovery after limb ischemia through stabilization of hypoxia-inducible factor 2α activity  Takuya Hashimoto,
Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity†
Heating is a multifunctional adjuvant that affects tumor microenvironment through several intrinsic and extrinsic mechanisms, which could enhance immunotherapy.
The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease
Potential role of hypoxia in development versus disease.
PK-M2 Makes Cells Sweeter on HIF1
Angiogenesis.
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD  Nupur Gupta, MD, Jay B. Wish, MD  American.
Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro
Hamid R. Rezvani, Nsrein Ali, Lars J
Hypoxia inducible factors in liver disease and hepatocellular carcinoma: Current understanding and future directions  Garrick K. Wilson, Daniel A. Tennant,
Angiogenesis and hepatocellular carcinoma
Figure 1 Involvement of pVHL in cellular physiology and RCC
Understanding the Importance of Smart Drugs in Renal Cell Carcinoma
Volume 76, Issue 9, Pages (November 2009)
Ahmed Mohyeldin, Tomás Garzón-Muvdi, Alfredo Quiñones-Hinojosa 
Hypoxia-inducible factor pathway and diseases of the vascular wall
The Hypoxic Response: Huffing and HIFing
Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects Akizawa et.
Volume 107, Issue 1, Pages 1-3 (October 2001)
Michael S. Dodd et al. BTS 2018;3:
In the name of God Zahra Barzang
Into Thin Air: How We Sense and Respond to Hypoxia
Insight from the Air–Skin Interface
Mutations of von Hippel-Lindau Tumor-Suppressor Gene and Congenital Polycythemia  Yves Pastore, Katerina Jedlickova, Yongli Guan, Enli Liu, James Fahner,
Endothelial Cells Form a Phalanx to Block Tumor Metastasis
Intratumoral hypoxia, radiation resistance, and HIF-1
Angiotensin II: breathtaking in the renal medulla
Inflammation and hypoxia in the kidney: friends or foes?
LIMD1 hypoxic induction occurs via HIF‐1 and facilitates formation of a hypoxic HIF‐1 degradation complex LIMD1 hypoxic induction occurs via HIF‐1 and.
Hypoxia and fibrosis in chronic kidney disease: crossing at pericytes
Volume 76, Issue 5, Pages (September 2009)
Niels Grote Beverborg et al. JCHF 2018;6:
PK-M2 Makes Cells Sweeter on HIF1
Schematic diagram of the HIF-signalling system and zebrafish homologues. Schematic diagram of the HIF-signalling system and zebrafish homologues. (A) Proteins.
Update on the Medical Treatment of Metastatic Renal Cell Carcinoma
ROS: Really involved in Oxygen Sensing
O2 Sensing: Only Skin Deep?
Vandetanib decreases tumor incidence and accumulation of HIF-2α, expression of c-Myc and growth factor receptors in the lung of hypoxic mice. Vandetanib.
Spearman’s rank correlation between preoperative serum levels of BNP/NT-proBNP and expression of HIF-2 alpha and preoperative serum level of VEGF. There.
Overall survival in all cases.
Presentation transcript:

Matt Macoul BMCB 658 4/6/2012

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

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

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

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

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

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), Peet, D., Hampton-Smith, R. (2007) Hypoxia-inducible factor. In AccessScience. Retrieved from