HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSION (English)

Clinical and Experimental Pharmacology and Physiology

The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen‐regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago.

Since the identification of EPO as the humoral regulator of red blood cell production and the cloning of the EPO gene, considerable progress has been made in understanding the regulation of EPO gene expression. This has finally led to the identification of a widespread cellular oxygen‐sensing mechanism. Central to this mechanism is the transcription factor complex hypoxia‐inducible factor (HIF)‐1.

The abundance and activity of HIF‐1, a heterodimer of an α‐ and β‐subunit, is predominantly regulated by oxygen‐dependent post‐translational hydroxylation of the α‐subunit. Non‐heme ferrous iron containing hydroxylases use dioxygen and 2‐oxoglutarate to specifically target proline and an asparagine residue in HIF‐1α. As such, the three prolyl hydroxylases (prolyl hydroxylase domain‐containing protein (PHD) 1, PHD2 and PHD3) and the asparagyl hydroxylase (factor inhibiting HIF (FIH)‐1) act as cellular oxygen sensors. In addition to erythropoiesis, HIF‐1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases.

In addition to the tight regulation by oxygen tension, temporal and tissue‐specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney.

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Table of contents – Volume 33, Issue 10

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

893
COMPUTER SIMULATIONS OF TRANSPORT THROUGH MEMBRANES: PASSIVE DIFFUSION, PORES, CHANNELS AND TRANSPORTERS
Tieleman, D Peter | 2006
904
ROLE OF HYPOTHALAMIC α2‐ADRENOCEPTOR ACTIVITY IN FRUCTOSE‐INDUCED HYPERTENSION
Mayer, Marcos A / Höcht, Christian / Opezzo, Javier AW / Peredo, Horacio A / Navacchia, Daniel / Taira, Carlos A / Fernández, Belisario E / Puyó, Ana M | 2006
904
ROLE OF HYPOTHALAMIC a2-ADRENOCEPTOR ACTIVITY IN FRUCTOSE-INDUCED HYPERTENSION
Mayer, M. A. / Hocht, C. / Opezzo, J. A. / Peredo, H. A. / Navacchia, D. / Taira, C. A. / Fernandez, B. E. / Puyo, A. M. | 2006
910
PARADOXICALLY ENHANCED HEART TOLERANCE TO ISCHAEMIA IN TYPE 1 DIABETES AND ROLE OF INCREASED OSMOLARITY
Chen, Hong / Shen, Wei‐Li / Wang, Xu‐Hui / Chen, Hong‐Zhuan / Gu, Jian‐Zhong / Fu, Jie / Ni, Ya‐Feng / Gao, Ping‐Jin / Zhu, Ding‐Liang / Higashino, Hideaki | 2006
917
EXTENT OF RENAL EFFECT OF CYCLO‐OXYGENASE‐2‐SELECTIVE INHIBITORS IS PHARMACOKINETIC DEPENDENT
Harirforoosh, Sam / Aghazadeh‐Habashi, Ali / Jamali, Fakhreddin | 2006
925
HEPATOPROTECTIVE AND HYPOLIPIDAEMIC EFFECTS OF GLYCOPROTEIN ISOLATED FROM GARDENIA JASMINOIDES ELLIS IN MICE
Lee, Sei‐Jung / Oh, Phil‐Sun / Lim, Kye‐Taek | 2006
934
DOCOSAHEXAENOIC ACID‐INDUCED PROTECTIVE EFFECT AGAINST IMPAIRED LEARNING IN AMYLOID β‐INFUSED RATS IS ASSOCIATED WITH INCREASED SYNAPTOSOMAL MEMBRANE FLUIDITY
Hashimoto, Michio / Hossain, Shahdat / Shimada, Toshio / Shido, Osamu | 2006
934
DOCOSAHEXAENOIC ACID-INDUCED PROTECTIVE EFFECT AGAINST IMPAIRED LEARNING IN AMYLOID b-INFUSED RATS IS ASSOCIATED WITH INCREASED SYNAPTOSOMAL MEMBRANE FLUIDITY
Hashimoto, M. / Hossain, S. / Shimada, T. / Shido, O. | 2006
940
CURCUMIN, THE ACTIVE PRINCIPLE OF TURMERIC (CURCUMA LONGA), AMELIORATES DIABETIC NEPHROPATHY IN RATS
Sharma, Sameer / Kulkarni, Shrinivas K / Chopra, Kanwaljit | 2006
946
PROSTAGLANDINS, CAPSAICIN‐SENSITIVE SENSORY NERVES AND NEUTROPHIL INFILTRATION, BUT NOT NITRIC OXIDE, CONTRIBUTE TO COLD RESTRAINT STRESS‐INDUCED GASTRIC ADAPTATION IN RATS
Tan, Ruken / Bülbül, Mehmet / Öngüt, Gözde / Tosun, Özgür / İzgüt‐Uysal, V Nimet | 2006
952
A PROTEOMIC ANALYSIS OF THE ACUTE EFFECTS OF HIGH‐INTENSITY EXERCISE ON SKELETAL MUSCLE PROTEINS IN FASTED RATS
Guelfi, Kym J / Casey, Tammy M / Giles, Jeffrey J / Fournier, Paul A / Arthur, Peter G | 2006
958
INTRODUCTION
Evans, Roger G / Denton, Kate M | 2006
961
RENAL OXYGEN DELIVERY: MATCHING DELIVERY TO METABOLIC DEMAND
O’Connor, Paul M | 2006
968
HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSION
Stockmann, Christian / Fandrey, Joachim | 2006
980
RENAL PARENCHYMAL OXYGENATION AND HYPOXIA ADAPTATION IN ACUTE KIDNEY INJURY
Rosenberger, Christian / Rosen, Seymour / Heyman, Samuel N | 2006
989
INTRARENAL OXYGENATION IN CHRONIC RENAL FAILURE
Norman, Jill T / Fine, Leon G | 2006
997
INTRARENAL OXYGEN IN DIABETES AND A POSSIBLE LINK TO DIABETIC NEPHROPATHY
Palm, Fredrik | 2006
1002
INTRARENAL OXYGEN AND HYPERTENSION
Welch, William J | 2006
1006
Scientific Writing: Easy When You Know How; Successful Scientific Writing: A Step‐by‐Step Guide for the Biological and Medical Sciences; Writing Successfully in Science
Ludbrook, John | 2006

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